Twenty-four patients with measurable metastatic renal cell carcinoma were treated in a phase I-II trial with alpha (human leukocyte) interferon (alpha IFN) and vinblastine (VBL) in combination. Patients received 3 X 10(6) IU/day of alpha IFN im 5 days/week and VBL iv weekly (at a starting dose of 0.15 mg/kg), with doses modified for toxicity. All patients were evaluable for toxicity; 23 patients were evaluable for response. An objective response rate of 13% was observed (three partial responses). An additional 22% of patients had minimal responses (five patients). The occurrence of nausea, vomiting, thrombocytopenia, hepatic dysfunction, and fever was comparable to that seen in previous studies of alpha IFN alone. Granulocytopenia, neurotoxicity, and malaise, however, occurred with increased frequency and severity. alpha IFN and VBL administered in combination in this dose schedule demonstrated activity similar to but toxicity greater than that seen in previous trials of alpha IFN alone.