Experimental results suggest synergistic activity of interferon with different cytotoxic agents, including vinblastine. Both interferon and vinblastine have shown synergistic activity against renal cell carcinoma in the human stem cell assay. In this multicenter phase II study, patients with documented advanced renal cell carcinoma were treated with interferon alpha-2a at a dose of 18 x 10(6) IU i.m. 3 days per week and vinblastine 0.1 mg/kg body weight i.v. every 3 weeks. Combination therapy was given for 6 months except patients with progressive disease. We observed 6/34 (17.6%) partial remissions and 16/34 (47%) no changes. Five out of six responses were seen in pulmonary metastases with a median response duration of 10 months and a median survival for the responders of 17 months. A dose reduction because of interferon toxicity was necessary in 60% of the treated patients. The main side effects were fever and influenza-like symptoms of different intensity in 70% of the patients, which decreased during the treatment periods. This trial demonstrates modest but definite antitumor activity of the combination of interferon alpha-2a/vinblastine. In comparison with single agent therapy we did not observe improved remission rates for the combination treatment.