Normal resident peritoneal macrophages from preleukemic AKR mice show considerable cytotoxicity against syngeneic AKR lymphoma cells but show little activity against L1210 and P388 cells. The cytotoxicity is inhibited in the presence of autologous serum. Macrophages obtained from C57Bl/6 and Balb-C mice show no cytotoxicity against AKR lymphoma cells. The macrophage cytotoxicity is augmented by rabbit anti-mouse thymocyte serum, thus account for the increased survival of AKR mice that received the antibody. The macrophage cytotoxicity declines as the mice aged to 6 months or older. Mice bearing large transplanted subcutaneous lymphoma have macrophages which are totally inactive against syngeneic lymphoma.