Renal-cell carcinoma rarely responds to cytotoxic chemotherapy, yet considerable evidence suggests that host factors may be capable of modifying the course of the disease. Although the mechanisms of interferon's antitumor effects are not well defined, the possibility that interferon might augment a host immune response provided a rationale for early clinical trials in this tumor. Investigations using various interferon alpha preparations (including interferons induced in human leukocytes and a human lymphoblastoid cell line) and recombinant interferons alfa-2a and alfa-2b have all provided evidence for antitumor activity. The overall major response rate with interferon alpha species in the 344 evaluable patients included in these 14 studies was 16.6% (57 patients), with response rates in individual studies ranging from 5% (1/21) to 31% (11/35). In renal-cell carcinoma, a response rate of the magnitude of 15% can be viewed with cautious optimism. Dose, schedule, route, and preparation have yet to be established for maximum efficacy, but progress has been made toward defining factors predicting response to treatment and mechanisms of interferon action.