Thirty-three patients with metastatic renal cell carcinoma were treated with recombinant human interferon gamma (rIFNγ) in two sequential, nonrandomized phase II studies. Fifteen patients received rIFNγby daily i.m. injection in doses ranging from 0.25 to 1.0 mg/m2, and 18 patients received it by daily continuous i.v. infusion in doses ranging from 0.01 to 0.05 mg/m2. Partial remissions were achieved by one of 14 (7%) evaluable patients in the i.m. study and in one of 16 in the i.v. study (6%). The incidence of clinical toxicity was similar for both studies. Toxicity was severe in patients receiving rIFNγby the i.m. route at 1.0 mg/m2and by the i.v. route at 0.05 mg/m2. Toxicity includes constitutional symptoms (fatigue, anorexia, weight loss), leukopenia, abnormalities in liver function tests, and hypertriglyceridemia. At the doses and schedules used, rIFNγhad minimal therapeutic activity as a single agent in metastatic renal cell carcinoma.