Cocaine was given to Balb/C mice by intramuscular injection to assess the effects of the drug on their immune system. An injection of 5 mg/kg of cocaine 24 hr before assay suppressed phagocytic activity of peritoneal macrophages and decreased the numbers of thymocytes and white blood cells in a dose-dependent manner. The suppression appeared to be reversible. Tumor-implanted mice received 10 consecutive days of injections of smaller doses of cocaine (0.05, 0.25, or 5 mg/kg), also resulting in a dose-dependent suppression of phagocytosis 24 hr after the last injection. Cocaine decreased the number of plaque-forming cells when 5 mg/kg of cocaine was injected on the day of immunization but no inhibition was detected if the drug was given later. The size of tumors appeared to be increased in mice injected with cocaine for 10 consecutive days in comparison to the control mice. The effects were concentration dependent. Our study showed that cocaine had general suppressive effects on the mouse immune system.