Biological response modifiers (BRMs) are agents or approaches that modify the relationship between the tumor and host by modifying the host's biological responses to tumor cells, with resultant therapeutic effects. BRMs include immunomodulators and components of the immune system, e.g. cytokines, antibodies and effector cells. A central challenge in the development of BRMs for therapy of cancer patients is to determine the main mechanism of action of each agent and by monitoring for effects of treatment on the key parameters, optimize the treatment protocol. The experience to date with interferons and with interleukin-2 (IL-2) is summarized, to illustrate both the promise of BRMs and the difficulties in determining the optimal therapeutic regimen and in turn this potential for more effective treatment of cancer. A new sequence of clinical trials for clinical evaluation of BRMs is described, with an emphasis on treatment of patients with minimal tumor burden.