A total of 49 patients with metastatic renal cell cancer underwent recombinant interferon-alpha 2a therapy combined with chemotherapy. Before therapy the patients without nephrectomy underwent angioinfarction of the primary renal tumor. Combined treatment included interferon at 5 x 10(6) units per m.2 intramuscularly daily, 5-fluorouracil at 750 mg./m.2 daily by continuous infusion intravenously (days 1 to 5) and mitomycin C at 5 mg./m.2 per day intravenously (days 1 and 2) repeated every 28 days. Of the patients 17 (35%, 95% confidence interval 22 to 49%) responded, and all 17 had partial remission that lasted a median of 7.1 months (range 4.2 to 20.9+ months). Response rate differed by metastatic sites: lung 46% (18 of 39 patients), lymph nodes 46% (6 of 13), mediastinum 20% (2 of 10) and liver 18% (2 of 11). Grade 3 to 4 toxicity (World Health Organization) included neutropenia (79% of the patients), thrombocytopenia (45%), stomatitis (34%), diarrhea (8%), nausea (18%) and central nervous system disorders (18%). The overall 35% response rate suggests that the combination of interferon-alpha 2a, 5-fluorouracil and mitomycin C is synergistic. Future studies are needed to confirm this finding and to assess the role of mitomycin C.