content: <PAGE>   1
     As filed with the Securities and Exchange Commission on December 16, 1997
                                                   Registration No. 333-__________
  ================================================================================
  
                         SECURITIES AND EXCHANGE COMMISSION
                               Washington, D.C. 20549
  
                              --------------------
  
                                      FORM S-8
                               REGISTRATION STATEMENT
                                       UNDER
                             THE SECURITIES ACT OF 1933
  
                              --------------------
  
                                  XENOMETRIX, INC.
               ------------------------------------------------------
               (Exact name of registrant as specified in its charter)
  
                                       
          DELAWARE                                      04-3166089
  (State of Incorporation)                 (I.R.S. Employer of Identification No.)
  
                                2425 N. 55TH STREET
                              BOULDER, COLORADO  80301
                                   (303) 447-1773
           -------------------------------------------------------------
           (Address and telephone number of principal executive offices)
  
                       AMENDED AND RESTATED STOCK OPTION PLAN
                   1993 NON-EMPLOYEE DIRECTORS STOCK OPTION PLAN
                   ---------------------------------------------
                             (Full title of the plans)
  
                                 RONALD L. HENDRICK
                  EXECUTIVE VICE PRESIDENT OF OPERATIONS, FINANCE
                  AND ADMINISTRATION, AND CHIEF FINANCIAL OFFICER
                                  XENOMETRIX, INC.
                                2425 N. 55TH STREET
                             BOULDER, COLORADO   80301
                                   (303) 447-1773
   ------------------------------------------------------------------------------
   (Name, address, including zip code, and telephone number, including area code,
                               of agent for service)
  
                              --------------------
  
                                     Copies to:
                             JAMES C.T. LINFIELD, ESQ.
                                 COOLEY GODWARD LLP
                          2595 CANYON BOULEVARD, SUITE 250
                          BOULDER, COLORADO    80302-6737
                                   (303) 546-4000 
  
                              --------------------
  
  <PAGE>   2
                          CALCULATION OF REGISTRATION FEE
  
  <TABLE>
  <CAPTION>
  ======================================================================================================================
                                                       PROPOSED MAXIMUM         PROPOSED MAXIMUM
    TITLE OF SECURITIES         AMOUNT TO BE          OFFERING PRICE PER       AGGREGATE OFFERING         AMOUNT OF
     TO BE REGISTERED            REGISTERED                SHARE (1)                PRICE (1)          REGISTRATION FEE
  ----------------------------------------------------------------------------------------------------------------------
  <S>                           <C>                   <C>                      <C>                     <C>
  Stock Options and                820,955                  $4.125                 $2,183,106                $644
  Common Stock (par
  value $.001)
  ======================================================================================================================
  </TABLE>
  
  (1)      Estimated solely for the purpose of calculating the amount of the
           registration fee, pursuant to Rule 457(h) under the Securities Act of
           1933, as amended (the "Act")   The offering price per share and
           aggregate offering price are based on (a) the weighted average
           exercise price for shares subject to options and stock previously
           granted under the Registrant's Amended and Restated Stock Option Plan,
           as amended and (b) the price per share and aggregate offering price
           based upon the closing price of Registrant's Common Stock on December
           9, 1997 as reported on the Nasdaq Small-Cap Market for options and
           shares to be granted under the Amended and Restated Stock Option Plan
           and 1993 Non-Employee Directors Stock Option Plan, as amended.  The
           following chart illustrates the calculation of the registration fee:
  
  <TABLE>
  <CAPTION>
  ======================================================================================================================
      TYPE OF SHARES           NUMBER OF SHARES        OFFERING PRICE PER       AGGREGATE OFFERING     REGISTRATION FEE
                                                              SHARE                   PRICE
  ----------------------------------------------------------------------------------------------------------------------
  <S>                      <C>                        <C>                    <C>                       <C>
  Shares issuable          362,542                    $4.125 (a)             $1,495,486                $441
  pursuant to options
  outstanding under the
  Amended and Restated
  Stock Option Plan, as
  amended
  ----------------------------------------------------------------------------------------------------------------------
  Shares issuable upon
  exercise of options      258,413                    $1.50 (b)              387,620                   114
  available for grant
  under the Amended and
  Restated Stock Option
  Plan, as amended
  ----------------------------------------------------------------------------------------------------------------------
  Shares issuable upon
  exercise of options      200,000                    $1.50 (b)              300,000                   89
  available for grant
  under the 1993 Non-
  Employee Directors
  Stock Option Plan, as
  amended
  ======================================================================================================================
  </TABLE>
  
           (a)     Weighted average exercise price.
           (b)     Nasdaq Small-Cap Market closing price of the Registrant's
                   Common Stock on December 10, 1997.
  
  ================================================================================
  
           Approximate date of commencement of proposed sale to the public:  As
  soon as practicable after this Registration Statement becomes effective.
  
  
  
  
  
                                         2.
  <PAGE>   3
  
  
  
                      INCORPORATION BY REFERENCE OF CONTENTS
                OF REGISTRATION STATEMENT ON FORM S-8 NO. 33-80889
  
           The contents of Registration Statement on Form S-8 No. 33-80889 filed
  with the Securities and Exchange Commission on December 26, 1995 are
  incorporated by reference herein.
  
                                      EXHIBITS
  
       EXHIBIT
       NUMBER
       -------
       5.1            Opinion of Cooley Godward LLP.
  
       10.30          Amendment to Registrant's Amended and Restated  Stock
                      Option Plan.
  
       10.31          Amendment to Registrant's 1993 Non-Employee Directors Stock
                      Option Plan.
  
       23.1           Consent of Price Waterhouse LLP.
  
       23.2           Consent of Cooley Godward LLP is contained in Exhibit 5.1
                      to this Registration Statement.
  
       24.1           Power of Attorney is contained on the signature pages.
  
  
  
  
  
                                         3.
  <PAGE>   4
  
  
  
                                     SIGNATURES
  
           Pursuant to the requirements of the Securities Act of 1933, as
  amended, the Registrant certifies that it has reasonable grounds to believe
  that it meets all of the requirements for filing on Form S-8 and has duly
  caused this Registration Statement to be signed on its behalf by the
  undersigned, thereunto duly authorized, in the City of Boulder, State of
  Colorado, on December 16, 1997.
  
                                         XENOMETRIX, INC.
  
  
  
                                         By:  /s/ Ronald L. Hendrick       
                                              -----------------------------------
                                              Ronald L. Hendrick
                                              Executive Vice President of 
                                              Operations, Finance and 
                                              Administration, and Chief Financial
                                              Officer
  
  
  
                                 POWER OF ATTORNEY
  
           KNOW ALL PERSONS BY THESE PRESENTS, that each person whose signature
  appears below constitutes and appoints Stephen J. Sullivan and Ronald L.
  Hendrick, and each or any one of them, his true and lawful attorney-in-fact and
  agent, with full power of substitution and resubstitution, for him and in his
  name, place and stead, in any and all capacities, to sign any and all
  amendments (including post-effective amendments) to this Registration
  Statement, and to file the same, with all exhibits thereto, and other documents
  in connection therewith, with the Securities and Exchange Commission, granting
  unto said attorneys-in-fact and agents, and each of them, full power and
  authority to do and perform each and every act and thing requisite and
  necessary to be done in connection therewith, as fully to all intents and
  purposes as he might or could do in person, hereby ratifying and confirming all
  that said attorneys-in-fact and agents, or any of them, or their or his
  substitutes or substitute, may lawfully do or cause to be done by virtue
  hereof.
  
  
  
  
  
                                         4.
  <PAGE>   5
  
  
  
           Pursuant to the requirements of the Securities Act of 1933, this
  Registration Statement has been signed by the following persons in the
  capacities and on the dates indicated.
  
  <TABLE>
  <CAPTION>
  SIGNATURE                                           TITLE                                  DATE
              <S>                                     <C>                                        <C>
               /s/ Stephen J. Sullivan                Chief Executive Officer, President         December 16, 1997
  -----------------------------------------------     and Director (Principal Executive
                 Stephen J. Sullivan                  Officer)                         
                                                      
  
  
                /s/ Ronald L. Hendrick                Executive Vice President of                December 16, 1997
  -----------------------------------------------     Operations, Finance and            
                  Ronald L. Hendrick                  Administration, and Chief Financial
                                                      Officer (Principal Financial and   
                                                      Accounting Officer)                
                                                                                         
                                                      
  
               /s/ Walter M. Lovenberg                Director                                   December 16, 1997
  -----------------------------------------------
                 Walter M. Lovenberg
  
  
              /s/ John K.A. Prendergast               Director                                   December 16, 1997
  -----------------------------------------------
                John K.A. Prendergast
  
  
               /s/ Randal P. Schumacher               Director                                   December 16, 1997
  -----------------------------------------------
                 Randal P. Schumacher
  
  
                /s/ Ralph Z. Sorenson                 Director                                   December 16, 1997
  -----------------------------------------------
                  Ralph Z. Sorenson
  
  </TABLE>
  
  
  
  
                                         5.
  <PAGE>   6
  
  
  
                                  EXHIBIT INDEX
  
  
  EXHIBIT
  NUMBER                     DESCRIPTION                   SEQUENTIAL PAGE NUMBER
  
  5.1         Opinion of Cooley LLP.
  
  10.30       Amendment to Registrant's Amended and 
              Restated Stock Option Plan.
  
  10.31       Amendment to 1993 Registrant's Non-Employee 
              Directors Stock Option Plan.
  
  23.1        Consent of Price Waterhouse LLP.
  
  23.2        Consent of Cooley Godward LLP is contained 
              in  Exhibit 5.1 to this Registration Statement.
  
  24.1        Power of Attorney is contained on the 
              signature pages.
metadata_documents: [{"type": "S-8", "sequence": "1", "description": "FORM S-8", "secsgml_size_bytes": 12507}]
metadata_filer: {"company-data": {"conformed-name": "XENOMETRIX INC \\DE\\", "cik": "0001000370", "assigned-sic": "3826", "irs-number": "043166089", "state-of-incorporation": "DE", "fiscal-year-end": "0630"}, "filing-values": {"form-type": "S-8", "act": "33", "file-number": "333-42381", "film-number": "97739290"}, "business-address": {"street1": "2425 NORTH 55TH ST", "street2": "STE 111", "city": "BOULDER", "state": "CO", "zip": "80301", "phone": "3034471773"}, "mail-address": {"street1": "2425 N 55TH ST", "street2": "STE 111", "city": "BOULDER", "state": "CO", "zip": "80301"}}
text: 1
     As filed with the Securities and Exchange Commission on December 16, 1997
                                                   Registration No. 333-__________
  ================================================================================
  
                         SECURITIES AND EXCHANGE COMMISSION
                               Washington, D.C. 20549
  
                              --------------------
  
                                      FORM S-8
                               REGISTRATION STATEMENT
                                       UNDER
                             THE SECURITIES ACT OF 1933
  
                              --------------------
  
                                  XENOMETRIX, INC.
               ------------------------------------------------------
               (Exact name of registrant as specified in its charter)
  
                                       
          DELAWARE                                      04-3166089
  (State of Incorporation)                 (I.R.S. Employer of Identification No.)
  
                                2425 N. 55TH STREET
                              BOULDER, COLORADO  80301
                                   (303) 447-1773
           -------------------------------------------------------------
           (Address and telephone number of principal executive offices)
  
                       AMENDED AND RESTATED STOCK OPTION PLAN
                   1993 NON-EMPLOYEE DIRECTORS STOCK OPTION PLAN
                   ---------------------------------------------
                             (Full title of the plans)
  
                                 RONALD L. HENDRICK
                  EXECUTIVE VICE PRESIDENT OF OPERATIONS, FINANCE
                  AND ADMINISTRATION, AND CHIEF FINANCIAL OFFICER
                                  XENOMETRIX, INC.
                                2425 N. 55TH STREET
                             BOULDER, COLORADO   80301
                                   (303) 447-1773
   ------------------------------------------------------------------------------
   (Name, address, including zip code, and telephone number, including area code,
                               of agent for service)
  
                              --------------------
  
                                     Copies to:
                             JAMES C.T. LINFIELD, ESQ.
                                 COOLEY GODWARD LLP
                          2595 CANYON BOULEVARD, SUITE 250
                          BOULDER, COLORADO    80302-6737
                                   (303) 546-4000 
  
                              --------------------
  2
                          CALCULATION OF REGISTRATION FEE
  ======================================================================================================================
                                                       PROPOSED MAXIMUM         PROPOSED MAXIMUM
    TITLE OF SECURITIES         AMOUNT TO BE          OFFERING PRICE PER       AGGREGATE OFFERING         AMOUNT OF
     TO BE REGISTERED            REGISTERED                SHARE (1)                PRICE (1)          REGISTRATION FEE
  ----------------------------------------------------------------------------------------------------------------------
  Stock Options and                820,955                  $4.125                 $2,183,106                $644
  Common Stock (par
  value $.001)
  ======================================================================================================================
  (1)      Estimated solely for the purpose of calculating the amount of the
           registration fee, pursuant to Rule 457(h) under the Securities Act of
           1933, as amended (the "Act")   The offering price per share and
           aggregate offering price are based on (a) the weighted average
           exercise price for shares subject to options and stock previously
           granted under the Registrant's Amended and Restated Stock Option Plan,
           as amended and (b) the price per share and aggregate offering price
           based upon the closing price of Registrant's Common Stock on December
           9, 1997 as reported on the Nasdaq Small-Cap Market for options and
           shares to be granted under the Amended and Restated Stock Option Plan
           and 1993 Non-Employee Directors Stock Option Plan, as amended.  The
           following chart illustrates the calculation of the registration fee:
  ======================================================================================================================
      TYPE OF SHARES           NUMBER OF SHARES        OFFERING PRICE PER       AGGREGATE OFFERING     REGISTRATION FEE
                                                              SHARE                   PRICE
  ----------------------------------------------------------------------------------------------------------------------
  Shares issuable          362,542                    $4.125 (a)             $1,495,486                $441
  pursuant to options
  outstanding under the
  Amended and Restated
  Stock Option Plan, as
  amended
  ----------------------------------------------------------------------------------------------------------------------
  Shares issuable upon
  exercise of options      258,413                    $1.50 (b)              387,620                   114
  available for grant
  under the Amended and
  Restated Stock Option
  Plan, as amended
  ----------------------------------------------------------------------------------------------------------------------
  Shares issuable upon
  exercise of options      200,000                    $1.50 (b)              300,000                   89
  available for grant
  under the 1993 Non-
  Employee Directors
  Stock Option Plan, as
  amended
  ======================================================================================================================
  (a)     Weighted average exercise price.
           (b)     Nasdaq Small-Cap Market closing price of the Registrant's
                   Common Stock on December 10, 1997.
  
  ================================================================================
  
           Approximate date of commencement of proposed sale to the public:  As
  soon as practicable after this Registration Statement becomes effective.
  
                                         2.
  3
  
                      INCORPORATION BY REFERENCE OF CONTENTS
                OF REGISTRATION STATEMENT ON FORM S-8 NO. 33-80889
  
           The contents of Registration Statement on Form S-8 No. 33-80889 filed
  with the Securities and Exchange Commission on December 26, 1995 are
  incorporated by reference herein.
  
                                      EXHIBITS
  
       EXHIBIT
       NUMBER
       -------
       5.1            Opinion of Cooley Godward LLP.
  
       10.30          Amendment to Registrant's Amended and Restated  Stock
                      Option Plan.
  
       10.31          Amendment to Registrant's 1993 Non-Employee Directors Stock
                      Option Plan.
  
       23.1           Consent of Price Waterhouse LLP.
  
       23.2           Consent of Cooley Godward LLP is contained in Exhibit 5.1
                      to this Registration Statement.
  
       24.1           Power of Attorney is contained on the signature pages.
  
                                         3.
  4
  
                                     SIGNATURES
  
           Pursuant to the requirements of the Securities Act of 1933, as
  amended, the Registrant certifies that it has reasonable grounds to believe
  that it meets all of the requirements for filing on Form S-8 and has duly
  caused this Registration Statement to be signed on its behalf by the
  undersigned, thereunto duly authorized, in the City of Boulder, State of
  Colorado, on December 16, 1997.
  
                                         XENOMETRIX, INC.
  
                                         By:  /s/ Ronald L. Hendrick       
                                              -----------------------------------
                                              Ronald L. Hendrick
                                              Executive Vice President of 
                                              Operations, Finance and 
                                              Administration, and Chief Financial
                                              Officer
  
                                 POWER OF ATTORNEY
  
           KNOW ALL PERSONS BY THESE PRESENTS, that each person whose signature
  appears below constitutes and appoints Stephen J. Sullivan and Ronald L.
  Hendrick, and each or any one of them, his true and lawful attorney-in-fact and
  agent, with full power of substitution and resubstitution, for him and in his
  name, place and stead, in any and all capacities, to sign any and all
  amendments (including post-effective amendments) to this Registration
  Statement, and to file the same, with all exhibits thereto, and other documents
  in connection therewith, with the Securities and Exchange Commission, granting
  unto said attorneys-in-fact and agents, and each of them, full power and
  authority to do and perform each and every act and thing requisite and
  necessary to be done in connection therewith, as fully to all intents and
  purposes as he might or could do in person, hereby ratifying and confirming all
  that said attorneys-in-fact and agents, or any of them, or their or his
  substitutes or substitute, may lawfully do or cause to be done by virtue
  hereof.
  
                                         4.
  5
  
           Pursuant to the requirements of the Securities Act of 1933, this
  Registration Statement has been signed by the following persons in the
  capacities and on the dates indicated.
  SIGNATURE                                           TITLE                                  DATE
  /s/ Stephen J. Sullivan                Chief Executive Officer, President         December 16, 1997
  -----------------------------------------------     and Director (Principal Executive
                 Stephen J. Sullivan                  Officer)                         
                                                      
  
                /s/ Ronald L. Hendrick                Executive Vice President of                December 16, 1997
  -----------------------------------------------     Operations, Finance and            
                  Ronald L. Hendrick                  Administration, and Chief Financial
                                                      Officer (Principal Financial and   
                                                      Accounting Officer)                
                                                                                         
                                                      
  
               /s/ Walter M. Lovenberg                Director                                   December 16, 1997
  -----------------------------------------------
                 Walter M. Lovenberg
  
              /s/ John K.A. Prendergast               Director                                   December 16, 1997
  -----------------------------------------------
                John K.A. Prendergast
  
               /s/ Randal P. Schumacher               Director                                   December 16, 1997
  -----------------------------------------------
                 Randal P. Schumacher
  
                /s/ Ralph Z. Sorenson                 Director                                   December 16, 1997
  -----------------------------------------------
                  Ralph Z. Sorenson
  5.
  6
  
                                  EXHIBIT INDEX
  
  EXHIBIT
  NUMBER                     DESCRIPTION                   SEQUENTIAL PAGE NUMBER
  
  5.1         Opinion of Cooley LLP.
  
  10.30       Amendment to Registrant's Amended and 
              Restated Stock Option Plan.
  
  10.31       Amendment to 1993 Registrant's Non-Employee 
              Directors Stock Option Plan.
  
  23.1        Consent of Price Waterhouse LLP.
  
  23.2        Consent of Cooley Godward LLP is contained 
              in  Exhibit 5.1 to this Registration Statement.
  
  24.1        Power of Attorney is contained on the 
              signature pages.