Immunologic changes were monitored in 5 patients with metastatic renal cell carcinoma participating in a phase II trial of recombinant interferon gamma (rIFN gamma). Treatment consisted of a 4-week period of intravenous infusion of either 0.1 mg/m2 given over 4 h on alternate days (3 times/week) or 2 mg/m2 given over 1 h for 5 days every other week. One minor response was seen at the higher dose level and toxicity was minimal (grades I-II). Absolute leukocyte counts and lymphocyte subpopulations did not change significantly. Both natural killer cytolytic activity and spontaneous monocyte-mediated tumoricidal activity increased. Prostaglandin E2 synthesis of patient leukocytes was abnormally high and pretreatment levels dropped during treatment. Data suggest that rIFN gamma may be potentially useful for enhancing immunologic function in renal cell carcinoma.