We have demonstrated that a murine cytotoxic peritoneal cell can be elicited by intraperitoneal immunization with heat-killed Mycobacterium bovis, strain Bacillus Calmette-Guérin (BCG). When these cells are injected together with cells of clone B(5)59 of B16 melanoma in a Winn-type transfer assay into syngeneic C57BL/6J mice, the tumorigenic potential of the melanoma is completely abrogated. Similarly, mice immunized intraperitoneally with dead BCG are protected against intraperitoneal challenge with a number of B16 melanoma cells sufficient to cause tumors in 100% of control mice. However, mice immunized intraperitoneally with dead BCG are not protected against tumor formation when B16 melanoma cells are injected subcutaneously. Co-injection of BCG-elicited peritoneal cells with B16 melanoma cells into nude or sublethally irradiated (650 rad) mice inhibits tumor formation in > 85% of the mice, indicating that additional participation of host bone marrow- or thymus-derived leukocytes is not required to eradicate the tumor implant. The effector cell in the BCG-induced peritoneal exudate is adherent and phagocytic and is a mononuclear phagocyte. Nonadherent lymphoid cells from the same BCG-induced peritoneal exudate and from thioglycollate-broth-elicited granylocytes and macrophages neither prevent nor delay B16 tumor formation.