Thirty-three patients with measurable metastatic renal cell carcinoma were entered into 2 consecutive phase II protocols using interferon alfa-2a. In protocol I, 20 patients were treated with interferon alfa-2a at a dose of 36 x I06 IU i.m. t.i.w. Vinblastine was also given t o 18 of these patients at a dose of 0.10-0.15 mg/kg i.v. every 2-3 weeks, depending on the blood cell count. In protocol 2, 13 patients received interferon alfa-2a at a dose of 18 x lo6 IU i.m. t.i.w. with stepwise dose escalations of 3 x lo6 IU being given every 2 weeks t o 8 patients. Vinblastine, at a dose of 0.1 mg/kg every 3 weeks, was also given t o I2 patients in protocol 2. Partial responses were seen in a total of 9 evaluable patients (lung, 5; lymph nodes, 2; liver, I; and bone, I), comprising 6 of 18 from protocol I and 3 of I3 from protocol 2. The median response duration was 89 days (range 91-540). No clinical parameter could be identified which was predictive for response. The subjective toxicity (flu-like symptoms and muscle pain) was considerable and necessitated dose reduction in I9 patients from protocol I. The dose schedule of protocol 2 was tolerated better even after slight dose escalation. The considerable interpatient variation in toxicity, however, made any demonstration of a clear dose-toxicity relationship impossible. High dose interferon treatment of metastatic renal cell carcinoma combined with vinblastine results in a 33% response rate (95% confidence interval: I1-55%). Moderate doses of interferon and vinblastine result in a 23% response rate (95% confidence interval: 0-46%). The role of vinblastine remains t o be determined.