Both natural killer cell- and macrophage-mediated spontaneous in vitro cytotoxicity for tumor targets is rapidly and strongly augmented by interferon. Macrophage-activating lymphokines considerably enhance macrophage-tumoricidal activity but did not affect natural killer cell-type cytotoxicity. Augmentation of cytolytic capacity by interferon and by macrophage-activating lymphokines is prevented by the tumor-promoting phorbol ester, 12-O-tetradecanoylphorbol-13-acetate. However, the classical antiviral activity and the specific binding of interferon to cell surface receptors remains unaffected by 12-O-tetradecanoylphorbol-13-acetate.