Via Facsimile and U.S. Mail
Mail Stop 6010


										September 9,
2005


B. Lynne Parshall, Esq.
Executive Vice President
Isis Pharmaceuticals, Inc.
1896 Rutherford Road
Carlsbad, California 92008

Re:	Isis Pharmaceuticals, Inc.
	Registration Statement on Form S-3
      Filed September 7, 2005
	File Number 333-128156

Dear Ms. Parshall:
      This is to advise you that we have undertaken a limited
review
of the above referenced registration statement to resolution of
your
pending confidential treatment request.  After any issues that
arise
during our examination of the request have been satisfied, we will
consider your request for acceleration of the effective date of
the
registration statement.

      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.

*	*	*

      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 Rules 460 and 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.

      Please contact Albert Lee at (202) 551-3654 or me at (202)
551-
3715 with any questions.

      Sincerely,



								Jeffrey P. Riedler
								Assistant Director

cc:	Julie M. Robinson, Esq.
	Cooley Godward LLP
	4401 Eastgate Mall
	San Diego, CA 92121

B. Lynne Parshall
Isis Pharmaceuticals, Inc.
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