Three sequential studies of alpha interferon were performed in a total of 84 evaluable patients with metastatic renal cell carcinoma. In Study I, conducted from 1981 to 1982, 43 patients received human leukocyte alpha interferon (IFN alpha) 3 X 10(6) U/day, 5 days per week for 12 weeks. In Study II, performed in 1983, vinblastine (0.1 mg/kg/week) was added to the same IFN alpha regimen in 22 subjects. Study III, held from 1984 to 1985, evaluated the effects of escalating doses of interferon alfa-2a (from 3 to 36 X 10(6) U/day) administered 5 days per week to 19 patients. Overall, complete (CR) and partial responses (PR) totaled 17% (14%, 14%, and 26% in Studies I-III, respectively). Median survival of all patients was 49 weeks. Median survival appeared to be superior in the third study, likely because of the patient mix (skewed toward a Karnofsky performance status of 10, disease-free interval longer than 1 year, and disease confined to the lung). Those prognostic factors were also found to correlate with improved median survival in the total group of 84 patients. Likewise, response to therapy was linked to prolonged survival; patients with CR, PR, or minimal responses had a median survival of 72 weeks. In all the favorable subgroups, responders had better outcomes than nonresponders, but it was not clear whether response to therapy merely selected out patients with better initial prognoses or actually led to improved survival.