Twenty-six patients with metastatic renal cell carcinoma (RCC) were treated in a phase I-II trial with recombinant interferon alpha-2b (alpha-IFN) and vinblastine (VBL) in combination. Patients received IFN at a starting dose of 3 x 10(6) IU/m2 subcutaneously three times a week and VBL 0.1 mg/kg intravenously every 3 weeks, with dose modification for toxicity. All patients were evaluable for toxicity; 18 patients were evaluable for efficacy. An objective response rate of 44% was observed (eight of 18 patients, with one complete response and seven partial responses). The median duration of response was 5 months. The actuarial survival of responding patients was significantly longer than that of nonresponding patients. In general, the toxicity was tolerable; the subjective toxicity and fever were similar to that reported for the same doses of IFN alone. Only a mild neurotoxicity, usually mixed polyneuropathy, occurred with increased frequency. Alpha-IFN and VBL administered at low doses in combination demonstrated the highest response rate so far reported in RCC without significant toxicity.