Antitumor effects of interleukin-2 entrapped in liposomes (IL-2 liposomes) on Renca, murine renal cell carcinoma of spontaneous origin, were evaluated by in vivo and in vitro experiments. As a local treatment model, IL-2 liposomes at a dose of 1.0 x 10(4) units were for 7 days injected adjacent to the Renca tumors inoculated in the back of BALB/c mice. The treatment inhibited the tumor growth and prolonged the survival time of mice significantly compared to the control (p < 0.01). Serum IL-2 levels after subcutaneous administration of IL-2 liposomes confirmed its slow releasing mechanism into blood circulation. The spleen cells from mice following the IL-2 liposome treatment showed higher cytotoxicity in vitro than that of IL-2 alone using Renca, YAC-1, and P-815 cells, which was determined by 51Cr-release assay. Indirect immunoperoxidase staining of tumor-infiltrating lymphocytes (TILs) showed that accumulation of Lyt-2+ and L3T4+ cells were seen in the tumor treated with IL-2 liposomes. These results indicate that IL-2 liposomes have a long-acting cytotoxicity against renal cell carcinoma caused by a slow release mechanism generated through the efficient local immune response mediated by TILs.