We evaluated the response rate and the immunorestorative properties of subcutaneously administered interferon-alpha 2b (IFN-alpha 2b) in patients with advanced renal cell carcinoma (RCC) and melanoma (MEL) and correlated the immune status with clinical responses. Thirty-five patients with advanced RCC and 12 with MEL were treated with recombinant IFN-alpha 2b. The dose was increased progressively from 5 x 10(6) IU the first week to 10 x 10(6) IU the second week and thereafter 15 x 10(6) IU subcutaneously. The response rate for RCC patients was as follows: (1) 6 patients achieved partial responses; (2) 9 patients had stable disease, and (3) 20 patients progressed. The response rate for patients with MEL was as follows: (1) 4 patients experienced partial response and (2) 8 patients progressed. In all patients blood was withdrawn prior to IFN treatment and then monthly. T lymphocytes after isolation from peripheral blood were tested for proliferation in the autologous mixed lymphocyte reaction (auto-MLR), and allogeneic mixed lymphocyte reaction (allo-MLR), interleukin-2 production (IL-2prod), expression of IL-2 receptors (IL-2rec) during the allo-MLR, and interleukin-1 production (IL-1prod) by peripheral blood monocytes. Striking increases were demonstrated in all parameters 1 month after treatment with IFN-alpha 2b. Patients with RCC experiencing a partial response showed a mean increase of 50% in the auto-MLR, 95% in the allo-MLR, 62% IL-2prod, 88% IL-2rec and 76% in IL-1prod.(ABSTRACT TRUNCATED AT 250 WORDS)