Conventional therapy for renal cell carcinoma using interleukin 2 (IL-2) has shown limited antitumor action. The purpose of our study was to investigate synergistic antitumor effects of IL-2 and Xiao-Chai-Hu-Tang (XCHT), and to elucidate the mechanisms of interaction between the two drugs against the murine renal cell carcinoma cell line, Renca, in vivo. The treatment was started 5 days after subcutaneous transplantation of Renca tumor. XCHT was given at a dose of 2.5 g/kg daily for 30 days orally. IL-2 was given at a dose of 10(4) U/mouse by subcutaneous injection every other day 8 times. Combination of XCHT and IL-2 inhibited growth of the tumor and prolonged survival significantly as compared with the untreated mice. Increased cellular infiltration was observed in tumor tissue and the lungs of mice treated with XCHT alone and by combination of XCHT and IL-2, but there were no histological changes in the liver and kidney. Elevation of serum IL-6 was observed in tumor-bearing mice, but IL-6 was significantly suppressed by administration of XCHT. The results obtained suggest that combination of XCHT and IL-2 induces enhanced immunological reaction in specific organs and tissues, and IL-6 may have a role in the synergistic effect of these two agents. It was concluded that combination of XCHT and IL-2 is useful in the treatment of patients with renal cell carcinoma.