We examined whether caffeine enhances the antitumor activity of adriamycin (ADR), in terms of prolonging survival in Ehrlich ascites carcinoma(ascites-type)-bearing mice. After administration of ADR at a dose of 0.5 mg/kg/d for 5d together with caffeine (100 mg/kg/d x 5 d), the survival period was increased by 39%. However, caffeine had little effect on this ADR induced-prolongation of survival following administration of ADR at 2.0 mg/kg/d for 4 d. Although a significant increase in ADR concentration in the ascites tumor was seen after administration of ADR at a dose of 0.5 mg/kg, caffeine failed to increase ADR concentration in the ascites tumor after administration of ADR at a dose of 2.0 mg/kg. The effect of caffeine thus appears to be due to its effect on the tumor distribution of ADR.