Twenty-seven patients with evaluable metastatic cancer were treated with recombinant interleukin-2 (rIL-2) and escalating doses of interferon gamma (IFN-gamma). rIL-2 was infused over a 15 min period at a constant dose (8 x 10(6) IU/m2/8 h x 5 days first cycle, and 8 x 10(6) IU/m2/12 h x 5 days second and third cycles, with 9 days rest between each cycle). IFN-gamma was started 4 days before each cycle of rIL-2 and was given every other day at a dosage of 1 x 10(6) U/m2 x 3/cycle (four patients), 5 x 10(6) U/m2 x 3/cycle (four patients), 5 x 10(6) U/m2 x 5/cycle (four patients) and 10 x 10(6) U/m2 x 5/cycle (15 patients). Common side effects were fluid retention and hepatic toxicity (27 and 15% grade greater than or equal to 2); one ischemic chest pains and one acute respiratory distress occurred. Toxicities were not greater than those described with high dose rIL-2 alone and were similar in each dose level of IFN-gamma. No patient died from the procedure. Four patients responded, one complete response and three partial responses; all were treated with 25 or 50 x 10(6) U/m2/cycle of IFN-gamma (melanoma, two patients; renal cell carcinoma, one patient; lymphoma, one patient). Further phase II studies at these dosages are justified to precisely define the antitumoral efficacy of this association.