Fifty-three patients with metastatic-renal cell carcinoma received treatment with combinations of recombinant alpha (rIFN-alpha-2a) and gamma (rIFN-gamma) interferons on three different treatment schedules. On treatment schedule A, 13 patients received i.m. rIFN-alpha-2a and rIFN-gamma simultaneously at a 1:1 ratio by dose units (2 X 10(6) U/m2), equivalent to a 1:10 ratio by protein weight. Results included severe constitutional symptoms in 62% of the patients and no partial remissions (PR) or complete remissions among 10 evaluable patients. On treatment schedule B, 25 patients received an i.m. injection of rIFN-alpha-2a and rIFN-gamma simultaneously at a 1:1 ratio by protein weight (2 X 10(6) U/m2 and 2 X 10(5) U/m2, respectively). This schedule was well tolerated, allowing a 25-50% increment in over 75% of the patients. Four patients (16%) achieved PR. On treatment schedule C, 15 patients received alternating weekly therapy: first rIFN-gamma (5 X 10(6) U/m2 daily for 7 days) followed by rIFN-alpha-2a (10 X 10(6) U/m2 daily for 7 days). One of 13 evaluable patients in treatment schedule C achieved an 80% tumor reduction and was rendered free of disease after the primary tumor was resected. Toxicity was similar in nature to that of rIFN-alpha-2a or rIFN-gamma separately. The toxicity of treatment schedule A suggested additive toxic effects. No distinct synergistic antitumor effect was observed.