The effect of systemic administration of Interleukin 2 (IL2) on intravesical Bacillus Calmette-Guerin (BCG) therapy was studied in an established murine bladder tumor, MBT-2. BCG (100 micrograms.) was administered intravesically on days 7 and 14 after seeding bladders with MBT-2 cells. IL2 (5,000 U/injection) was given intraperitoneally every eight hours for 10 times (days seven through 10 and 14 through 17). BCG or IL2 therapy alone failed to reduce incidence of tumor implantation and tumor weight; whereas, combined treatment with BCG and IL2 reduced tumor weight significantly compared to saline or BCG treated mice. Cytotoxicity was assessed in a four-hour 75Semethionine-release assay. Augmentation of natural killer cell activity was only observed in mice treated with BCG plus IL2. MBT-2 target cells were not lysed by spleen cells from mice treated with BCG or saline. IL2 therapy produced lymphokine-activated killer cell activity, though combining BCG with IL2 suppressed this activity after each course of treatment. The results suggest that combined treatment with IL2 enhances the therapeutic effect of BCG therapy. However, this enhancement of antitumor activity is not clearly explained by augmentation of natural killer or in vivo-generated lymphokine-activated killer cells.