<PAGE>


As filed with the Securities and Exchange Commission on September 28, 2000
                                               Registration No. 333-___________
===============================================================================

                       SECURITIES AND EXCHANGE COMMISSION
                             Washington, D.C. 20549
                              --------------------
                                    FORM S-3
                             REGISTRATION STATEMENT
                                      Under
                           THE SECURITIES ACT OF 1933
                              --------------------

                         THE IMMUNE RESPONSE CORPORATION
             (Exact name of registrant as specified in its charter)

            Delaware                                       33-0255679
-------------------------------                 -------------------------------
(State or other jurisdiction of                         (I.R.S. Employer
 incorporation or organization)                        Identification No.)

                                5935 Darwin Court
                           Carlsbad, California 92008
                                 (760) 431-7080
                 ---------------------------------------------
                   (Address, including zip code, and telephone
                  number, including area code, of registrant's
                          principal executive offices)

       DENNIS J. CARLO, Ph.D.                             Copies to:
President and Chief Executive Officer             THOMAS E. SPARKS, JR., ESQ.
   The Immune Response Corporation                  KARLA W. FRANKLIN, ESQ.
          5935 Darwin Court                           ALAN G. SMITH, ESQ.
     Carlsbad, California 92008                  Pillsbury Madison & Sutro LLP
           (760) 431-7080                               P. O. Box 7880
                                                 San Francisco, CA 94120-7880
                                                        (415) 983-1000

            (Name, address, including zip code, and telephone number,
                   including area code, of agent for service)

Approximate date of commencement of proposed sale to the public: From time to
time after the effective date of this Registration Statement as determined by
the selling stockholders.

If the only securities being registered on this Form are being offered pursuant
to dividend or interest reinvestment plans, please check the following box: / /

If any of the securities being registered on this Form are to be offered on a
delayed or continuous basis pursuant to Rule 415 under the Securities Act of
1933, other than securities offered only in connection with dividend or interest
reinvestment plans, please check the following box. / /

If this Form is filed to register additional securities for an offering pursuant
to Rule 462(b) under the Securities Act, please check the following box and list
the Securities Act registration statement number of the earlier effective
registration statement for the same offering. / /

If this Form is a post-effective amendment filed pursuant to Rule 462(c) under
the Securities Act, check the following box and list the Securities Act
registration statement number of the earlier effective registration statement
for the same offering. / /

If delivery of the prospectus is expected to be made pursuant to Rule 434,
please check the following box. / /

<TABLE>
<CAPTION>
                                        CALCULATION OF REGISTRATION FEE
==========================================================================================================================
   Title of Each                                            Proposed               Proposed
Class of Securities                     Amount To        Maximum Offering      Maximum Aggregate          Amount of
 To Be Registered                     Be Registered     Price Per Share(1)     Offering Price(1)       Registration Fee
--------------------------------------------------------------------------------------------------------------------------
<S>                                 <C>                 <C>                    <C>                     <C>
Common Stock, $.0025 par value      1,317,609 shares          $7.56                $9,961,124              $2,629.74
==========================================================================================================================
</TABLE>

(1) Estimated  solely for the purpose of calculating the  registration  fee
    pursuant  to Rule  457(c),  based upon the  average of the high and low
    price reported on the Nasdaq National Market on September 22, 2000.

<PAGE>

The registrant hereby amends this Registration Statement on such date or dates
as may be necessary to delay its effective date until the Registrant shall file
a further amendment which specifically states that this Registration Statement
shall thereafter become effective in accordance with Section 8(a) of the
Securities Act of 1933 or until the Registration Statement shall become
effective on such date as the Commission, acting pursuant to said Section 8(a),
may determine.


<PAGE>

         The information in this prospectus is not complete and may be changed.
The selling stockholder may not sell these securities under this prospectus
until the registration statement filed with the Securities and Exchange
Commission is effective. This prospectus is not an offer to sell these
securities and is not soliciting an offer to buy these securities in any state
where the offer or sale is not permitted.

         Subject to Completion, Dated September 28, 2000


                         THE IMMUNE RESPONSE CORPORATION
                        1, 317,609 Shares of Common Stock

                                 --------------

         This prospectus is part of a registration statement we filed with the
Securities and Exchange Commission, which will be used by the selling
stockholder, identified on page 12, to resell the common stock. This means:

         -      The selling stockholder may sell its shares of common stock from
                time to time.

         -      For information on the methods of sale of the common stock, you
                should refer to the section entitled "Plan of Distribution" on
                page 12. We will not receive any portion of the proceeds from
                the sale of these shares.

         -      You should read this prospectus and any prospectus supplement
                carefully before you invest.

         Our common stock is listed on the Nasdaq National Market under the
symbol "IMNR." On September 27, 2000, the last reported sale price for our
common stock on the Nasdaq National Market was $7.25 per share.

                                 --------------

         INVESTING IN OUR COMMON STOCK INVOLVES RISKS. SEE "RISK FACTORS"
BEGINNING ON PAGE 2.

         NEITHER THE SECURITIES AND EXCHANGE COMMISSION NOR ANY STATE SECURITIES
COMMISSION HAS APPROVED OR DISAPPROVED THESE SECURITIES OR PASSED UPON THE
ADEQUACY OF THIS PROSPECTUS. ANY REPRESENTATION TO THE CONTRARY IS A CRIMINAL
OFFENSE.

                                 --------------

                The date of this Prospectus is ____________, 2000


                                      -1-
<PAGE>


RISK FACTORS

         YOU SHOULD CAREFULLY CONSIDER THE RISKS DESCRIBED BELOW BEFORE MAKING
AN INVESTMENT DECISION. THE RISKS AND UNCERTAINTIES DESCRIBED BELOW ARE NOT THE
ONLY ONES FACING US. ADDITIONAL RISKS AND UNCERTAINTIES NOT PRESENTLY KNOWN TO
US OR THAT WE CURRENTLY DEEM IMMATERIAL MAY ALSO IMPAIR OUR BUSINESS.

         IF ANY OF THE FOLLOWING RISKS ACTUALLY OCCUR, OUR BUSINESS COULD BE
ADVERSELY AFFECTED. IN THOSE CASES, THE TRADING PRICE OF OUR COMMON STOCK COULD
DECLINE, AND YOU MAY LOSE ALL OR PART OF YOUR INVESTMENT.

OUR FAILURE TO DEVELOP AND COMMERCIALIZE PRODUCTS SUCCESSFULLY MAY CAUSE US TO
CEASE OPERATIONS

         We have not completed the development of any products. Our failure to
develop and commercialize products successfully may cause us to cease
operations. Our potential therapies under development will require significant
additional research and development efforts and regulatory approvals prior to
potential commercialization.

         The discontinuation of a previous Phase 3 trial of REMUNE in May 1999
due to lack of efficacy has had a material adverse effect on us. If our primary
marketing partner, Agouron Pharmaceuticals, Inc., or Agouron, a Pfizer Inc.
Company, does not successfully complete the current pivotal trial of REMUNE we
may have to abandon REMUNE or seek additional funding.

         Our other therapies and technologies are at earlier stages of
development than REMUNE and may not be shown to be safe or efficacious or ever
receive regulatory approval. Some of our technologies have not yet been tested
in humans. Human testing of potential products based on these technologies may
not be permitted by regulatory authorities. Even if human testing is permitted,
the products based on these technologies may not be successfully developed or be
shown to be safe and efficacious.

         The results of our preclinical studies and clinical trials may not be
indicative of future clinical trial results. A commitment of substantial
resources to conduct time-consuming research, preclinical studies and clinical
trials will be required if we are to develop any products. Delays in planned
patient enrollment in our clinical trials may result in increased costs, program
delays or both. None of our potential products may prove to be safe and
effective in clinical trials. Food and Drug Administration, or FDA, or other
regulatory approvals may not be obtained and even if successfully developed and
approved, our products may not achieve market acceptance. Any products resulting
from our programs are not expected to be successfully developed or commercially
available for a number of years, if at all.

         Unacceptable toxicities or side effects may occur at any time in the
course of human clinical trials or, if any products are successfully developed
and approved for marketing, during commercial use of our products. The
appearance of any unacceptable toxicities or side effects could interrupt,
limit, delay or abort the development of any of our products or, if previously
approved, necessitate their withdrawal from the market.


                                      -2-
<PAGE>

OUR  ADDITIONAL  FINANCING  REQUIREMENTS  AND LIMITED  ACCESS TO  FINANCING  MAY
ADVERSELY AFFECT OUR ABILITY TO DEVELOP PRODUCTS

         We will need to raise additional funds to conduct research and
development, preclinical studies and clinical trials necessary to bring our
potential products to market and to establish manufacturing and marketing
capabilities. A failure to raise additional funds would require us to scale back
or eliminate some or all of our research and development programs or license to
third parties products or technologies that we would otherwise seek to develop
ourselves. We estimate that our existing capital resources and available
equipment financing will be sufficient to fund our current and planned
operations through 2001.

         Although we anticipate that development of REMUNE will continue to
represent a significant portion of our overall expenditures, we also anticipate
that costs related to the development of REMUNE will decrease in 2000. Other
anticipated costs with respect to REMUNE will depend on many factors, in
particular the continuation of our collaboration with Agouron.

         Our future capital requirements will depend on many factors, including:

         -      continued scientific progress in our research and development
                programs;

         -      the scope and results of preclinical studies and clinical
                trials;

         -      the time and costs involved in obtaining regulatory approvals;

         -      the costs involved in filing, prosecuting and enforcing patent
                claims;

         -      competing technological and market developments;

         -      the cost of manufacturing scale-up;

         -      effective commercialization activities and arrangements; and

         -      other factors not within our control.

IF AGOURON TERMINATES ITS COLLABORATION WITH US WE MAY HAVE TO ABANDON REMUNE

         According to its terms, our binding letter of intent with Agouron may
be terminated at will and at any time by Agouron. The termination of our
agreement with Agouron might require us to abandon REMUNE. Agouron has been
acquired by Pfizer Inc. We do not know which Agouron research products, if any,
Pfizer Inc. will continue to fund in the future.

WE MAY BE UNABLE TO ENTER INTO ADDITIONAL COLLABORATIONS OR MAINTAIN EXISTING
ONES

         We intend to seek additional collaborative arrangements to develop and
commercialize our products. We may not be able to negotiate collaborative
arrangements on favorable terms, or at all, in the future and our current or
future collaborative arrangements may not be successful or continue. Under the
Schering collaboration, Schering's obligation to fund expired on

                                      -3-
<PAGE>


December 31, 1999. Without funding arrangements, we may have to abandon some of
our products under development.

OUR PATENTS AND PROPRIETARY TECHNOLOGY MAY NOT PROVIDE US WITH ANY BENEFIT AND
THE PATENTS AND PROPRIETARY TECHNOLOGY OF OTHERS MAY PREVENT US FROM
COMMERCIALIZING PRODUCTS

         A failure to obtain meaningful patent protection for our potential
products and processes would greatly diminish the value of our potential
products and processes.

         In addition, whether or not our patents are issued, or issued with
limited coverage, others may receive patents which contain claims applicable to
our products. We are aware that AstraZeneca PLC has acquired the rights to a
patent, which has been issued in Europe and other countries, that may interfere
with our ability to develop some of our technologies related to autoimmune
disease if the patent is upheld after current opposition proceedings. This
patent, and others that we are not aware of, may adversely affect our ability to
develop and commercialize products.

         The patent positions of biotechnology and pharmaceutical companies can
be highly uncertain and involve complex legal and factual questions. Therefore,
the breadth of claims allowed in biotechnology and pharmaceutical patents cannot
be predicted. We also rely upon unpatented trade secrets and know how, and
others may independently develop substantially equivalent trade secrets or know
how.

         We also rely on protecting our proprietary technology in part through
confidentiality agreements with our corporate collaborators, employees,
consultants and certain contractors. These agreements may be breached and we may
not have adequate remedies for any breach. In addition, our trade secrets may
otherwise become known or independently discovered by our competitors.

         Our products and processes may infringe, or be found to infringe on,
patents not owned or controlled by us, such as the patent owned by
AstraZeneca PLC. If relevant claims of third-party patents are upheld as
valid and enforceable, we could be prevented from practicing the subject
matter claimed in the patents, or would be required to obtain licenses or
redesign our products or processes to avoid infringement. Licenses may not be
available at all or on commercially reasonable terms and we may not be able
to redesign our products or processes to avoid infringement.

         Litigation may be necessary to defend against claims of infringement,
to enforce our patents or to protect trade secrets. Litigation could result in
substantial costs and diversion of management efforts regardless of the results
of the litigation. An adverse result in litigation could subject us to
significant liabilities to third parties, require disputed rights to be licensed
or require us to cease using certain technologies.

                                      -4-
<PAGE>


OUR HISTORY OF OPERATING LOSSES AND OUR EXPECTATIONS OF CONTINUING LOSSES MAY
HURT OUR ABILITY TO CONTINUE OPERATIONS

         As of June 30, 2000 we had a consolidated accumulated deficit of $191.7
million. We have not generated revenues from the commercialization of any
product. We expect to incur substantial net operating losses over the next
several years, which may imperil our ability to continue operations. We may not
be able to generate sufficient product revenue to become profitable on a
sustained basis, or at all.

THE LENGTHY PRODUCT APPROVAL PROCESS AND UNCERTAINTY OF GOVERNMENT REGULATORY
REQUIREMENTS MAY DELAY OR PREVENT US FROM COMMERCIALIZING PRODUCTS

         Clinical testing, manufacture, promotion and sale of our products are
subject to extensive regulation by numerous governmental authorities in the
United States, principally the FDA, and corresponding state and foreign
regulatory agencies. This regulation may delay or prevent us from
commercializing products. Noncompliance with applicable requirements can result
in, among other things, fines, injunctions, seizure of products, total or
partial suspension of product marketing, failure of the government to grant
premarket approval, withdrawal of marketing approvals and criminal prosecution.

         The regulatory process for new therapeutic drug products, including the
required preclinical studies and clinical testing, is lengthy and expensive. We
may not receive necessary FDA clearances for any of our potential products in a
timely manner, or at all. The length of the clinical trial process and the
number of patients the FDA will require to be enrolled in the clinical trials in
order to establish the safety and efficacy of our products is uncertain.

         Even if additional clinical trials of REMUNE are successfully
completed, the FDA may not approve REMUNE for commercial sale. We may encounter
significant delays or excessive costs in our efforts to secure necessary
approvals. Regulatory requirements are evolving and uncertain. Future United
States or foreign legislative or administrative acts could also prevent or delay
regulatory approval of our products. We may not be able to obtain the necessary
approvals for clinical trials, manufacturing or marketing of any of our products
under development. Even if commercial regulatory approvals are obtained, they
may include significant limitations on the indicated uses for which a product
may be marketed.

         In addition, a marketed product is subject to continual FDA review.
Later discovery of previously unknown problems or failure to comply with the
applicable regulatory requirements may result in restrictions on the marketing
of a product or withdrawal of the product from the market, as well as possible
civil or criminal sanctions.

         Among the other requirements for regulatory approval is the requirement
that prospective manufacturers conform to the FDA's Good Manufacturing
Practices, or GMP. In complying with the FDA's GMP requirements, manufacturers
must continue to expend time, money and effort in production, record keeping and
quality control to assure that products meet applicable specifications and other
requirements. Failure to comply with the FDA's GMP requirements subjects
manufacturers to possible FDA regulatory action. We or our contract
manufacturers, if


                                      -5-
<PAGE>

any, may not be able to maintain compliance with the FDA's GMP requirements on
a continuing basis. Failure to maintain compliance could have a material adverse
effect on us.

         The FDA has not designated expanded access protocols for REMUNE as
"treatment" protocols. The FDA may not determine that REMUNE meets all of the
FDA's criteria for use of an investigational drug for treatment use. Even if
REMUNE is allowed for treatment use, third party payers may not provide
reimbursement for the costs of treatment with REMUNE.

         The FDA may not consider REMUNE or any other of our products under
development to be an appropriate candidate for accelerated approval, expedited
review or fast track designation.

         Marketing any drug products outside of the United States will subject
us to numerous and varying foreign regulatory requirements governing the design
and conduct of human clinical trials and marketing approval. Approval procedures
vary among countries and can involve additional testing, and the time required
to obtain approval may differ from that required to obtain FDA approval. Foreign
regulatory approval processes include all of the risks associated with obtaining
FDA approval set forth above, and approval by the FDA does not ensure approval
by the health authorities of any other country.

TECHNOLOGICAL CHANGE AND COMPETITION MAY RENDER OUR POTENTIAL PRODUCTS OBSOLETE

         The biotechnology industry continues to undergo rapid change and
competition is intense and is expected to increase. Competitors may succeed in
developing technologies and products that are more effective or affordable than
any that we are developing or that would render our technology and products
obsolete and noncompetitive. Many of our competitors have substantially greater
experience, financial and technical resources and production, marketing and
development capabilities than us. Accordingly, some of our competitors may
succeed in obtaining regulatory approval for products more rapidly or
effectively than us.

OUR LACK OF COMMERCIAL MANUFACTURING AND MARKETING EXPERIENCE MAY PREVENT US
FROM SUCCESSFULLY COMMERCIALIZING PRODUCTS

         We have not manufactured any of our product candidates in commercial
quantities. We may not successfully make the transition from manufacturing
clinical trial quantities to commercial production quantities or be able to
arrange for contract manufacturing and this could prevent us from
commercializing products. Even if REMUNE is successfully developed and receives
FDA approval, we have not demonstrated the capability to manufacture REMUNE in
commercial quantities. Except for REMUNE, we have not demonstrated the ability
to manufacture our treatments in large-scale clinical quantities either. We rely
on a third party for the final inactivation step of the REMUNE manufacturing
process. If the existing manufacturing operations prove inadequate, there can be
no assurance that any arrangement with a third party can be established on a
timely basis, or that we can establish other manufacturing capacity on a timely
basis.

         We have no experience in the sales, marketing and distribution of
pharmaceutical products. Thus, our products may not be successfully
commercialized even if they are developed and approved for commercialization.


                                      -6-
<PAGE>

         The manufacturing process of our products involves a number of steps
and requires compliance with stringent quality control specifications imposed by
us and by the FDA. Moreover, our products can only be manufactured in a facility
that has undergone a satisfactory inspection by the FDA. For these reasons, we
would not be able quickly to replace our manufacturing capacity if we were
unable to use our manufacturing facilities as a result of a fire, natural
disaster (including an earthquake), equipment failure or other difficulty, or if
such facilities are deemed not in compliance with the FDA's GMP requirements and
the non-compliance could not be rapidly rectified. Our inability or reduced
capacity to manufacture our products would prevent us from successfully
commercializing products.

         We may enter into arrangements with contract manufacturing companies to
expand our own production capacity in order to meet requirements for our
products, or to attempt to improve manufacturing efficiency. If we choose to
contract for manufacturing services and encounter delays or difficulties in
establishing relationships with manufacturers to produce, package and distribute
our finished products, clinical trials, market introduction and subsequent sales
of the products would be delayed. Further, contract manufacturers must also
operate in compliance with the FDA's GMP requirements; failure to do so could
result in, among other things, the disruption of product supplies. Our potential
dependence upon third parties for the manufacture of our products may adversely
affect our profit margins and our ability to develop and deliver products on a
timely and competitive basis.

ADVERSE DETERMINATIONS CONCERNING PRODUCT PRICING, REIMBURSEMENT AND RELATED
MATTERS COULD PREVENT US FROM SUCCESSFULLY COMMERCIALIZING PRODUCTS

         Our ability to earn sufficient returns on our products will depend in
part on the extent to which reimbursement for the costs of the products and
related treatments will be available from government health administration
authorities, private health coverage insurers, managed care organizations and
other organizations. Failure to obtain appropriate reimbursement could prevent
us from successfully commercializing products. Third party payors are
increasingly challenging the price of medical products and services. If
purchasers or users of our products are not able to obtain adequate
reimbursement for the cost of using the products, they may forego or reduce
their use. Significant uncertainty exists as to the reimbursement status of
newly approved health care products, and whether adequate third party coverage
will be available.

PRODUCT LIABILITY EXPOSURE MAY EXPOSE US TO SIGNIFICANT LIABILITY

         We face an inherent business risk of exposure to product liability and
other claims in the event that the development or use of our technology or
prospective products is alleged to have resulted in adverse effects. We may not
avoid significant liability exposure. We may not have sufficient insurance
coverage and we may not be able to obtain sufficient coverage at a reasonable
cost. An inability to obtain product liability insurance at acceptable cost or
to otherwise protect against potential product liability claims could prevent or
inhibit the commercialization of our products. A product liability claim could
hurt our financial performance. Even if we avoid liability exposure, significant
costs could be incurred that could hurt our financial performance.


                                      -7-

<PAGE>

HAZARDOUS MATERIALS AND ENVIRONMENTAL MATTERS COULD EXPOSE US TO SIGNIFICANT
COSTS

         Although we do not currently manufacture commercial quantities of our
product candidates, we produce limited quantities of these products for our
clinical trials. We may be required to incur significant costs to comply with
current or future environmental laws and regulations. Our research and
development processes involve the controlled storage, use and disposal of
hazardous materials, biological hazardous materials and radioactive compounds.
We are subject to federal, state and local laws and regulations governing the
use, manufacture, storage, handling and disposal of these materials and some
waste products. Although we believe that our safety procedures for handling and
disposing of these materials comply with the standards prescribed by these laws
and regulations, the risk of accidental contamination or injury from these
materials cannot be completely eliminated. In the event of an accident, we could
be held liable for any damages that result, and any liability could exceed our
resources. Our operations, business or assets may be materially and adversely
affected by current or future environmental laws or regulations.

SUBORDINATION OF COMMON STOCK TO PREFERRED STOCK COULD HURT COMMON STOCKHOLDERS

         Our common stock is expressly subordinate to our Series F Convertible
Preferred Stock in the event of our liquidation, dissolution or winding up. If
we were to cease operations and liquidate our assets, there may not be any
remaining value available for distribution to the holders of common stock after
providing for the Series F Convertible Preferred Stock liquidation preference.

YOU COULD SUFFER SUBSTANTIAL DILUTION OF YOUR INVESTMENT IF OUR PREFERRED STOCK
IS CONVERTED INTO COMMON STOCK OR CERTAIN OPTIONS OR WARRANTS TO PURCHASE COMMON
STOCK ARE EXERCISED

         In 1998 we sold 200 shares of Series F Convertible Preferred Stock, or
Series F Stock, in return for gross proceeds of $10 million. These shares of
Series F Stock are currently convertible into at least 2.4 million shares of our
common stock, which number is subject to increase if our common stock does not
meet certain specified price trading levels. Additionally, on April 24, 2001 we
will be required to redeem the Series F Stock in either cash or in shares of our
common stock. Further, as of March 31, 2000 we had reserved 6.3 million shares
of our common stock for potential issuances upon the exercise of stock options
and warrants and payment of dividends on the Series F Stock. Issuance of any of
these additional shares could substantially dilute your interest in our company.

VOLATILITY OF STOCK PRICE AND ABSENCE OF DIVIDENDS MAY HURT COMMON STOCKHOLDERS

         The market price of our common stock, like that of the common stock of
many other biopharmaceutical companies, has been and is likely to be highly
volatile. Factors such as the following could have a significant adverse impact
on the market price of our common stock:

         -      the results of preclinical studies and clinical trials by us,
                our collaborators or our competitors;

         -      concern as to, or other evidence of, the safety or efficacy of
                our products or our competitors' products;


                                      -8-
<PAGE>

         -      announcements of technological innovations or new products by us
                or our competitors;

         -      governmental regulatory actions;

         -      actual or anticipated changes in drug reimbursement policies;

         -      developments with our collaborators;

         -      developments concerning patent or other proprietary rights of
                ours or our competitors (including litigation);

         -      period-to-period fluctuations in our operating results;

         -      changes in estimates of our performance by securities analysts;

         -      market conditions for biopharmaceutical stocks in general; and

         -      other factors not within our control.

         We have never paid cash dividends on our common stock and do not
anticipate paying any cash dividends in the foreseeable future.

CHANGES TO FINANCIAL ACCOUNTING STANDARDS MAY AFFECT OUR REPORTED RESULTS OF
OPERATIONS

         We prepare our financial statements to conform with generally accepted
accounting principles, or GAAP. GAAP are subject to interpretation by the
American Institute of Public Accountants, the Securities and Exchange Commission
and various bodies formed to interpret and create appropriate accounting
policies. A change in those policies can have a significant effect on our
reported results and may even affect our reporting of transactions completed
before a change is announced. Accounting policies affecting many other aspects
of our business, including rules relating to purchase and pooling-of-interests
accounting for business combinations, employee stock option grants and revenue
recognition have recently been revised or are under review. Changes to those
rules or the questioning of current practices may adversely affect our reported
financial results or the way we conduct our business. In addition, our
preparation of financial statements in accordance with GAAP requires that we
make estimates and assumptions that affect the recorded amounts of assets and
liabilities, disclosure of those assets and liabilities and at the date of the
financial statements and the recorded amounts of expenses during the reporting
period. A change in the facts and circumstances surrounding those estimates
could result in a change to our estimates and could impact our future operating
results.

OUR CERTIFICATE OF INCORPORATION AND BYLAWS INCLUDE PROVISIONS THAT COULD
DISCOURAGE POTENTIAL TAKEOVER ATTEMPTS AND MAKE ATTEMPTS BY STOCKHOLDERS TO
CHANGE MANAGEMENT MORE DIFFICULT

         The approval of 66 2/3 percent of our voting stock is required to
approve certain transactions and to take certain stockholder actions, including
the calling of special meetings of


                                      -9-
<PAGE>

stockholders and the amendment of any of the anti-takeover provisions, such as
those providing for a classified board of directors, contained in our
certificate of incorporation. Further, pursuant to the terms of our stockholder
rights plan, we have distributed a dividend of one right for each outstanding
share of common stock. These rights will cause substantial dilution to the
ownership of a person or group that attempts to acquire us on terms not approved
by our Board of Directors and may have the effect of deterring hostile takeover
attempts. The practical effect of these provisions is to require a party seeking
control of our company to negotiate with the our Board of Directors, which could
delay or prevent a change in control. These provisions could limit the price
that investors might be willing to pay in the future for our common stock.

         We are subject to the anti-takeover provisions of Section 203 of the
Delaware General Corporation Law, which prohibits us from engaging in a
"business combination" with an "interested stockholder" for a period of three
years after the date of the transaction in which the person first becomes an
"interested stockholder," unless the business combination is approved in a
prescribed manner. The application of Section 203 also could have the effect of
delaying or preventing a change of control.

                       ADDITIONAL OR UPDATED RISK FACTORS

         Prior to making an investment decision with respect to the common stock
offered hereby, prospective investors should also carefully consider any
specific factors set forth under a caption "risk factors" in the applicable
prospectus supplement, if any, together with all of the other information
appearing in this prospectus or the prospectus supplement or incorporated by
reference into this prospectus.

               SPECIAL NOTE REGARDING FORWARD-LOOKING INFORMATION

         When used in this prospectus, the words "intends to," "believes,"
"anticipates," "expects" and similar expressions are intended to identify
forward-looking statements. These forward-looking statements are based largely
on our expectations and are subject to a number of risks and uncertainties, some
of which are beyond our control. For a discussion of some of these risks, see
"Risk Factors." These forward-looking statements speak only as of the date of
this prospectus. We expressly disclaim any obligation or undertaking to release
publicly any updates or revisions to any forward-looking statement contained
within this prospectus to reflect any change in our expectations with regard to
those forward-looking statements or any change in events, conditions or
circumstances on which any such statement is based.

                       WHERE YOU CAN FIND MORE INFORMATION

         We file annual, quarterly and special reports, proxy statements and
other information with the SEC. This information can be (1) read and copied at
the public reference facilities maintained by the SEC at 450 Fifth Street, N.W.,
Judiciary Plaza, Washington, D.C., and at the SEC's Chicago Regional Office, 500
West Madison Street, Chicago, Illinois; and New York Regional Office, 7 World
Trade Center, New York, New York and (2) accessed via a Web site maintained by
the SEC (http://www.sec.gov). Copies of the material can also be obtained from
the Public Reference Section of the SEC at 450 Fifth Street, N.W., Judiciary
Plaza, Washington, D.C. 20549 at prescribed rates. Please call the SEC at
1-800-SEC-0330 for further information on the public reference rooms.


                                      -10-
<PAGE>

         This prospectus is a part of a registration statement we filed with the
SEC. This prospectus does not contain all of the information set forth in the
registration statement. For more information about us and our common stock, you
should read the registration statement and its exhibits and schedules. Copies of
the registration statement, including its exhibits may be obtained from the
SEC's principal office in Washington, D.C. upon payment of the fees prescribed
by the SEC, or may be examined without charge at the offices of the SEC.

         The SEC allows us to "incorporate by reference" the information we file
with them, which means that we can disclose important information to you by
referring you to those documents. The information incorporated by reference is
considered to be part of this prospectus, and later information that we file
with the SEC will automatically update and supersede this information. We
incorporate by reference the documents listed below and any future filings made
by us with the SEC under Sections 13(a), 13(c), 14 or 15(d) of the Securities
Exchange Act of 1934 (File No. 0-18006):

         (a) Our Annual Report on Form 10-K for the year ended December 31,
             1999;

         (b) Our Quarterly Reports on Form 10-Q for the quarters ended March 31,
             2000 and June 30, 2000;

         (c) Our Current Report on Form 8-K dated March 15, 2000;

         (d) Our Current Report on Form 8-K dated August 7, 2000;

         (e) The description of our common stock set forth in the registration
             statement on Form 8-A filed on March 30, 1990; and

         (f) The description of the Preferred Stock Purchase rights for Series E
             Participating Preferred Stock, par value $0.001, set forth in the
             registration statement on Form 8-A filed on March 4, 1992.

         Upon written or oral request, we will provide without charge to each
person to whom a copy of this prospectus is delivered a copy of the documents
incorporated by reference into this prospectus (other than exhibits to these
documents unless the exhibits are specifically incorporated by reference into
those documents). Requests should be submitted in writing or by telephone at
(760) 431-7080 to The Immune Response Corporation, at our principal executive
offices, 5935 Darwin Court, Carlsbad, California 92008.

                                 USE OF PROCEEDS

         We will not receive any proceeds from the sale of common stock by the
selling stockholder in the offering.

              ISSUANCE OF COMMON STOCK TO THE SELLING STOCKHOLDERS

         We entered into a common stock purchase agreement with the selling
stockholder in June 1998, under which we received seven payments of $2 million
each for the purchase of shares of


                                      -11-
<PAGE>

our unregistered common stock. Pursuant to the common stock purchase agreement
we sold and issued 1,477,609 shares of our common stock to the selling
stockholder.

                            INCOME TAX CONSIDERATIONS

         You should consult your own tax advisor about the income tax issues and
the consequences of holding and disposing of our common stock.

                               SELLING STOCKHOLDER

         As of September 28, 2000 there was one selling stockholder as set
forth below. Share ownership information is based upon information supplied by
Agouron.

<TABLE>
<CAPTION>
                                                                                                Percentage of
                                                    Shares of Common                           Common Stock to
                                                     Stock Issuable        Number of            be Held After
                                                        Held at           Shares Being            Sale of
           Selling Stockholder                     September 28, 2000        Offered            Common Stock
------------------------------------------         ------------------    -----------------     ---------------
<S>                                                <C>                   <C>                   <C>
Agouron Pharmaceuticals, Inc..............         1,317,609             1,317,609                      0
</TABLE>


         We have a material relationship with the selling stockholder. During
June 1998, we entered into a collaborative agreement with the selling
stockholder, under which we exclusively licensed to the selling stockholder
the marketing rights to REMUNE in North America, Europe, Japan and certain
other countries. Pursuant to this agreement, if REMUNE receives regulatory
approval, we will manufacture commercial supplies of REMUNE and will share
with the selling stockholder profits from the commercialization of REMUNE on
a 50/50 basis. As part of the June 1998 agreement, the selling stockholders
agreed to make up to six quarterly payments of $3 million each for research
and development, of which all six payments have been received, and to make
additional payments upon achievement, if any, of certain milestones. We also
entered into the common stock purchase agreement with the selling stockholder
pursuant to which we received seven payments of $2 million each for the
purchase of shares of our unregistered common stock.

                              PLAN OF DISTRIBUTION

         The selling stockholder (or, subject to applicable law, its pledges,
donees, distributees, transferees or other successors in interest) may sell
shares from time to time in public transactions, on or off the Nasdaq National
Market, or private transactions, at prevailing market prices or at privately
negotiated prices, including but not limited to, one or any combination of the
following types of transactions:

         -      ordinary brokers' transactions;

         -      transactions involving cross or block trades or otherwise on the
                Nasdaq National Market;

         -      purchases by brokers, dealers or underwriters as principal and
                resale by those purchasers for their own accounts pursuant to
                this prospectus;


                                      -12-
<PAGE>

         -      "at the market," to or through market makers, or into an
                existing market for our common stock;

         -      in other ways not involving market makers or established trading
                markets, including the direct sales to purchasers or sales
                effected through agents;

         -      through transactions in options, swaps or other derivatives
                (whether exchange-listed or otherwise); or

         -      in privately negotiated transactions.

         In effecting sales, brokers or dealers engaged by the selling
stockholder may arrange for other brokers or dealers to participate in the
resales. The selling stockholder also may pledge the shares to a financial
institution, broker or dealer. Upon a default, the financial institution, broker
or dealer may effect sales of the pledged shares pursuant to this prospectus.

         Brokers, dealers or agents may receive compensation in the form of
commissions, discounts or concessions from selling the stock in amounts to be
negotiated in connection with the sale. The selling stockholder and any
participating brokers or dealers may be deemed to be "underwriters" within the
meaning of the Securities Act in connection with such sales. In such event, any
commission, discount or concession these "underwriters" receive may be deemed to
be underwriting compensation.

                                  LEGAL MATTERS

         The validity of the issuance of the shares offered in this prospectus
was passed upon for us by Pillsbury Madison & Sutro LLP, San Francisco,
California. A partner of Pillsbury Madison & Sutro LLP owns 15,000 shares of our
common stock and an option to acquire 20,000 shares of our common stock.

                                     EXPERTS

         The consolidated financial statements of The Immune Response
Corporation as of December 31, 1998 and 1999 and for each of the three years in
the period ended December 31, 1999 included in the Company's Annual Report on
Form 10-K and incorporated herein by reference have been audited by Arthur
Andersen LLP, independent public accountants, as indicated in their reports with
respect thereto, and are incorporated herein by reference in reliance upon the
authority of said firm as experts in giving said reports.


                                      -13-
<PAGE>

===============================================================================

         We have not authorized any dealer, salesperson or any other person to
give any information or to represent anything not contained in this prospectus.
You must not rely on any unauthorized information. This prospectus does not
offer to sell or seek an offer to buy any shares in any jurisdiction where it is
unlawful. The information contained in this prospectus is correct only as of the
date of this prospectus, regardless of the time of the delivery of this
prospectus or any sale of the shares.


                                TABLE OF CONTENTS


<TABLE>
<CAPTION>
                                                          Page
                                                          ----
<S>                                                       <C>
Risk Factors.................................................2
Additional or Updated Risk Factors..........................10
Special Note Regarding Forward-Looking Information..........10
Where You Can Find More Information.........................10
Use of Proceeds.............................................11
Issuance of Common Stock to the Selling
Stockholders................................................11
Income Tax Considerations...................................12
Selling Stockholders........................................12
Plan of Distribution........................................12
Legal Matters...............................................13
Experts.....................................................13
</TABLE>


                                1,317,609 Shares
                                  Common Stock



                                   THE IMMUNE
                              RESPONSE CORPORATION

                          ____________________________
                                   PROSPECTUS


                              _______________, 2000



===============================================================================

                                      -14-

<PAGE>


                                     PART II

                     INFORMATION NOT REQUIRED IN PROSPECTUS

ITEM 14.  OTHER EXPENSES OF ISSUANCE AND DISTRIBUTION

         The following table sets forth the various expenses in connection with
the sale and distribution of the securities being REGISTERED hereby, other than
underwriting discounts and commissions. All amounts are estimated except the
Securities and Exchange Commission registration fee and the Nasdaq National
Market listing fee.

<TABLE>
<CAPTION>
                                                                                         AMOUNT
                                                                                         ------
<S>                                                                                    <C>
SEC registration fee                                                                   $ 2,629.74
Accounting fees and expenses                                                             5,000.00
Legal fees and expenses                                                                 15,000.00
Registrar and transfer agent's fees                                                      2,500.00
NNM listing fee                                                                         17,500.00
Miscellaneous fees and expenses                                                          7,370.26
                                                                                       ----------
         Total                                                                         $50,000.00
</TABLE>


ITEM 15.  INDEMNIFICATION OF DIRECTORS AND OFFICERS

         Section 145 of the Delaware General Corporation Law, the "Delaware GCL,
permits our board of directors to indemnify any person against expenses
(including attorneys' fees), judgments, fines and amounts paid in settlement
actually and reasonably incurred by him in connection with any threatened,
pending or completed action, suit or proceeding in which such person is made a
party by reason of his being or having been a director, officer, employee or
agent of ours, in terms sufficiently broad to permit such indemnification under
certain circumstances for liabilities (including reimbursement for expenses
incurred) arising under the Securities Act of 1933, as amended (the "Act"). The
Delaware GCL provides that indemnification pursuant to its provisions is not
exclusive of other rights of indemnification to which a person may be entitled
under any by-law, agreement, vote of stockholders or disinterested directors, or
otherwise.

         Article VII of our Restated Certificate of Incorporation, as amended,
and Article V of our Bylaws, provide for indemnification of our directors,
officers, employees and other agents to the maximum extent permitted by law.

         In addition, we have entered into separate indemnification agreements
with our directors and officers that will require us, among other things, to
indemnify them against certain liabilities that may arise by reason of their
status or service as directors or officers to the fullest extent not prohibited
by law.


                                      II-1
<PAGE>

ITEM 16.  EXHIBITS

<TABLE>
<CAPTION>
         Exhibit
         Number                       Description of Document*
         -------                      ------------------------
         <S>         <C>
         5.1         Opinion of Pillsbury Madison & Sutro LLP regarding the
                     legality of the securities being registered.
         23.1        Consent of independent public accountants.
         23.2        Consent of Pillsbury Madison & Sutro LLP (included in its
                     opinion filed as Exhibit 5.1 to this Registration Statement).
         24.1        Power of Attorney (see page II-4).
</TABLE>

---------------
 *    Parenthetical references after description of exhibits relate to the
      exhibit number under which exhibits were initially filed.


ITEM 17.  UNDERTAKINGS

         Insofar as indemnification for liabilities arising under the Securities
Act of 1933, as amended (the "Act"), may be permitted to our directors, officers
and controlling persons pursuant to the foregoing provisions, or otherwise, we
have been advised that in the opinion of the Securities and Exchange Commission
such indemnification is against public policy as expressed in the Act and is,
therefore, unenforceable. In the event that a claim for indemnification against
such liabilities (other than the payment by us of expenses incurred or paid by a
director, officer or controlling person of ours in the successful defense of any
action, suit or proceeding) is asserted by such director, officer or controlling
person in connection with the securities being registered, we will, unless in
the opinion of our counsel the matter has been settled by controlling precedent,
submit to a court of appropriate jurisdiction the question whether such
indemnification by us is against public policy as expressed in the Act and will
be governed by the final adjudication of such issue.

         We hereby undertake:

                (1) To file during any period in which offers or sales are being
         made, a post-effective amendment to this registration statement; (i) to
         include any prospectus required by Section 10(a)(3) of the Act; (ii) to
         reflect in the prospectus any facts or events arising after the
         effective date of the registration statement (or the most recent
         post-effective amendment thereof) which, individually or in the
         aggregate, represent a fundamental change in the information set forth
         in this registration statement; and (iii) to include any material
         information with respect to the plan of distribution not previously
         disclosed in this registration statement or any material change to such
         information in this registration statement; provided, however, that
         paragraphs (i) and (ii) do not apply if the information required to be
         included in a post-effective amendment by those paragraphs is contained
         in


                                      II-2
<PAGE>

         periodic reports filed by us pursuant to Section 13 or Section 15(d)
         of the Securities Exchange Act of 1934, as amended (the "Exchange Act")
         that are incorporated by reference in this registration statement.

                (2) That, for the purpose of determining any liability under the
         Act, each post-effective amendment that contains a form of prospectus
         shall be deemed to be a new registration statement relating to the
         securities offered therein, and the offering of such securities at that
         time shall be deemed to be the initial bona fide offering thereof.

                (3) To remove from registration by means of a post-effective
         amendment any of the securities being registered which remain unsold at
         the termination of the offering.

                (4) For purposes of determining any liability under the Act,
         each filing of our annual report pursuant to Section 13(a) or Section
         15(d) of the Exchange Act which is incorporated by reference in this
         registration statement shall be deemed to be a new registration
         statement relating to the securities offered therein, and the offering
         of such securities at that time shall be deemed to be the initial bona
         fide offering thereof.



                                      II-3
<PAGE>


                                   SIGNATURES


         Pursuant to the requirements of the Securities Act of 1933, we certify
that we have reasonable grounds to believe that we meet all of the requirements
for filing on Form S-3, and have duly caused this registration statement to be
signed on our behalf by the undersigned, thereunto duly authorized, in the City
of Carlsbad, State of California, September 28, 2000.

                                     THE IMMUNE RESPONSE CORPORATION


                                     By /s/ Dennis J. Carlo
                                        ---------------------------------------
                                        Dennis J. Carlo, Ph.D.
                                        President and Chief Executive Officer



                                POWER OF ATTORNEY

         KNOW ALL MEN BY THESE PRESENTS, that the person whose signature appears
below constitutes and appoints Dennis J. Carlo, Ph.D. and Howard Sampson and
each of them, his true and lawful attorneys-in-fact and agents, each with full
power of substitution and resubstitution, for him and in his name, place and
stead, ian any and all capacities, to sign any and all amendments, including
post-effective amendments, to this registration statement, and to file the same,
with 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, as fully to all intents
and purposes as he might or could do in person, hereby ratifying and confirming
all that each of said attorneys-in-fact and agents or their substitute or
substitutes may lawfully do or cause to be done by virtue hereof.

         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/ Dennis J. Carlo
--------------------------------------         President, Chief Executive Officer,         September 28, 2000
       Dennis J. Carlo, Ph.D.                  Chief Scientific Officer and
                                               Director (Principal Executive
                                               Officer)

                                      II-4
<PAGE>

<CAPTION>
                 Signature                                     Title                              Date
                 ---------                                     -----                              ----
<S>                                            <C>                                         <C>

         /s/ Howard Sampson
--------------------------------------         Vice President, Finance, Chief              September 28, 2000
           Howard Sampson                      Financial Officer and Treasurer
                                               (Principal Financial and Principal
                                               Accounting Officer)
         /s/ James B. Glavin
--------------------------------------         Chairman of the Board of                    September 28, 2000
           James B. Glavin                     Directors



--------------------------------------         Director                                    September   , 2000
         Kevin B. Kimberlin


         /s/ Melvin Perelman
--------------------------------------         Director                                    September 28, 2000
           Melvin Perelman


         /s/ William M. Sullivan               Director                                    September 28, 2000
--------------------------------------
         William M. Sullivan



--------------------------------------         Director                                    September   , 2000
           Philip M. Young
</TABLE>

                                      II-5

<PAGE>

                                  EXHIBIT INDEX

<TABLE>
<CAPTION>
     Exhibit
     Number                        Description of Document
     -------                       -----------------------
     <S>             <C>
       5.1           Opinion of Pillsbury Madison & Sutro LLP regarding the
                     legality of the securities being registered.

      23.1           Consent of independent public accountants.

      23.2           Consent of Pillsbury Madison & Sutro LLP (included in its
                     opinion filed as Exhibit 5.1 to this Registration Statement).

      24.1           Power of Attorney (see page II-4).
</TABLE>