Eight patients with progressive metastatic renal cell carcinoma were selected for one course of subcutaneous recombinant interleukin-2 (IL-2) plus vinblastine (VBL) treatment lasting for seven weeks. Seven of the eight patients were evaluable for response, eight for toxicity. Peripheral blood lymphocytes (PBL) from the evaluable patients were isolated and frozen prior to, during, and after the treatment courses; kinetics of their cytolytic activity was assessed and compared under standard conditions in 51Cr microcytotoxicity assay with natural killer (NK)-sensitive and NK-resistant human tumor targets. Among the evaluable patients treated, there was 1 partial responder (10+ months, regressions occurred in lung, retroperitoneal lymph nodes and adrenal metastases) and 3 patients achieved a stable disease (10+, 10+, 5+ months). Systemic toxicity was mild to moderate with treatment-limiting adverse effects in one patient (severe thrombocytopenia, grade IV). In the IL-2-treated patients, the cytolytic activity of PBL directed against NK-sensitive targets rapidly decreased during the first week of IL-2 treatment, approaching the negative values on day 10. Then the cytolytic activity was slowly increasing and reached its maximum within another two weeks. Afterwards, the cytolytic activity of PBL was again decreasing and the approximate values of the initial cytolysis were reached after 6-8 weeks. In contrast, with NK-resistant targets such characteristic kinetics of PBL cytolytic activity was not observed. The kinetics of PBL-mediated cytolysis was similar in IL-2-responders and non-responders, so that no correlation of in vivo and in vitro effects of subcutaneous IL-2 and VBL treatment could be established.