Intraperitoneal inoculation of CF1 mice with Bacillus Calmette-Guérin (BCG) protected many of them against the ascites form of Ehrlich carcinoma; and, for those that developed cancer, complete regression occurred in up to 50% of the cases at an advanced state of the neoplastic disease. In contrast, when a booster dose of BCG was administered in admixture with tumor cells, the incidence of the tumor was lower and tumor regressions were very rarely observed in mice that developed cancer. Trypan blue, an inhibitor of lysosomal enzymes of macrophages, was found to markedly suppress the natural (innate) antitumor resistance of control mice as well as the acquired resistance and tumor regressions of BCG-sensitized mice. Moreover, a comparison of the cytotoxic activity of the adherent (macrophages) and nonadherent (predominantly lymphocytes) cells isolated from the peritoneal cavity of BCG-sensitized mice, as measured by the inhibition of DNA synthesis, revealed that the effector cells were amongst the macrophages. In contrast, spleen macrophages were devoid of cytotoxicity. The spleen lymphocytes from both BCG-sensitized and control mice possessed about the same significant cytotoxic activity. These results indicate that the activated peritoneal macrophages, induced by a local injection of BCG, could play an important role in the antitumor immunity against Ehrlich carcinoma.