SecProbe.io

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Mail Stop 4-6
								April 28, 2005

John P. McAlister, III
President and Chief Executive Officer
Tripos, Inc.
1699 South Hanley Road
St. Louis, MO  63144

	Re:    	Tripos, Inc.
		Registration Statement on Form S-1
		Filed April 1, 2005
		File No. 333-123742

Dear Mr. McAlister:

      We have limited our review of the above-referenced Form S-1
registration statement to the issues identified below.  Where
indicated, we think you should revise your document in response to
these comments.  If you disagree, we will consider your
explanation
as to why our comment is inapplicable or a revision is
unnecessary.
Please be as detailed as necessary in your explanation.  In some
of
our comments, we may ask you to provide us with supplemental
information so we may better understand your disclosure.  After
reviewing this information, we may or may not raise additional
comments.

      Please understand that the purpose of our review process is
to
assist you in your compliance with the applicable disclosure
requirements and to enhance the overall disclosure in your filing.
We welcome any questions you may have about our comments or on any
other aspect of our review and look forward to working with you.
Feel free to call us at the telephone numbers listed at the end of
this letter.

Recent Developments
1. You are seeking to register securities that you issued to
former
shareholders of Optive Research, Inc., which was acquired in
January
2005, and certain institutional investors pursuant to a purchase
agreement dated December 2004.  Disclosure of these transactions
appears in Forms 8-K, yet we are unable to locate the registration
rights agreement, if any, entered into with the former
shareholders
of Optive Research, or the December 2004 purchase agreement as
exhibits to any Forms 8-K or this S-1. Please advise.

Selling Shareholders
2. Please disclose the natural persons who exercise sole or shared
voting and/or investment power over Horizon Technology Funding
Company II LLC, Horizon Technology Funding Company III LLC and
Sand
Hill Venture Debt III, LLC.  This disclosure may be included in
the
footnotes to the table.  See interpretation 4S of the Regulation
S-K
portion of the March 1999 supplement to the publicly available CF
Telephone Interpretation manual, as well as interpretation I.60 of
the July 1997 version of the telephone interpretation manual.
3. Tell us whether any of the selling shareholders are affiliates
of
a registered broker-dealer. To the extent that any selling
shareholder is an affiliate of a broker-dealer, please disclose
this
in the footnotes to the selling shareholder table and disclose
whether the seller purchased the shares in the ordinary course of
business and at the time of the purchase of the securities to be
resold, the seller had any agreements or understandings, directly
or
indirectly, with any person to distribute the securities.

      We urge all persons who are responsible for the accuracy and
adequacy of the disclosure in the filings reviewed by the staff to
be
certain that they have provided all information investors require
for
an informed decision.  Since the company and its management are in
possession of all facts relating to a company`s disclosure, they
are
responsible for the accuracy and adequacy of the disclosures they
have made.

      Notwithstanding our comments, in the event the company
requests
acceleration of the effective date of the pending registration
statement, it should furnish a letter, at the time of such
request,
acknowledging that:

* 		should the Commission or the staff, acting pursuant to
delegated authority, declare the filing effective, it does not
foreclose the Commission from taking any action with respect to
the
filing;

*	the action of the Commission or the staff, acting pursuant to
delegated authority, in declaring the filing effective, does not
relieve the company from its full responsibility for the adequacy
and
accuracy of the disclosure in the filing; and

* 	the company may not assert this action as a defense in any
proceeding initiated by the Commission or any person under the
federal securities laws of the United States.

      In addition, please be advised that the Division of
Enforcement
has access to all information you provide to the staff of the
Division of Corporation Finance in connection with our review of
your
filing or in response to our comments on your filing.

      We will consider a written request for acceleration of the
effective date of the registration statement as a confirmation of
the
fact that those requesting acceleration are aware of their
respective
responsibilities under the Securities Act of 1933 and the
Securities
Exchange Act of 1934 as they relate to the proposed public
offering
of the securities specified in the above registration statement.
We
will act on the request and, pursuant to delegated authority,
grant
acceleration of the effective date.

      We direct your attention to Rule 461 regarding requesting
acceleration of a registration statement.  Please allow adequate
time
after the filing of any amendment for further review before
submitting a request for acceleration.  Please provide this
request
at least two business days in advance of the requested effective
date.

      Any questions should be directed to Maryse Mills-Apenteng at
(202) 942-1861.  If you need further assistance, you may contact
the
undersigned at 202-942-1800.

								Sincerely,

      			Barbara C. Jacobs
      			Assistant Director

cc:  	Via facsimile:  410-539-6981
	Thene M. Martin, Esq.
      Hogan and Hartson LLP
      111 South Calvert Street
      Baltimore, MD  21202

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Tripos, Inc.
April 28, 2005
Page 1 of 3

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