An attempt has been made to clarify immunosuppressive properties of anti-tumor agents by studying the effect of the agents on the thymus, the reticulo-endothelial system (RES) and hepatic drug-metabolizing enzyme activities of tumor (an ascites hepatoma, AH 130 cells)-bearing rats. A drastic decrease in the thymus weight and the total number of the lymphocytes and an enhanced activity of thymus alkaline phosphatase were detected by injecting either 5-fluorouracil (5FU) or cyclophosphamide (CP) (30 mg each/kg weight, i.p.) daily for 5 days to tumor-bearing rats. The agents, however, did not induce any conspicuous damage in microsomal mixed function oxidase system or the RES. The presence of 10-day-old tumor resulted in an extreme decrease in the weight and lymphocytes of thymus and a partial decrease in the microsomal drug metabolizing enzyme activities and the RES. Thus, these antitumor agents may lead to the decline of host-mediated immune mechanism. The multiplication of the tumor cells also appears to depress the immune functions and the host resistance.