More than two dozen cytokines are now available as recombinant proteins suitable for in vivo testing. Several of these novel biologic response modifiers have been evaluated in clinical trials, and a few have been proven to be effective. Interferon-α is often used to treat low-grade lympho- and myeloproliferative diseases, and it is undergoing evaluation as treatment of several solid tumors. Interleukin-2 was recently approved by the US Food and Drug Administration for the treatment of patients with metastatic renal cell carcinoma. Other cytokines that are active as antitumor agents in experimental animals have failed to enter the mainstream of oncologic practice because of poor results in preliminary trials and, in some instances, prohibitive toxicity. This review focuses on the cellular mechanisms underlying cytokine-induced tumor regression and toxicity.