Spleen (SC) and peritoneal cells (PC) from C57BL/6 mice immune to Listeria monocytogenes (LM) have a marked cytotoxic effect on the in vitro growth of B-16 melanoma. Cytotoxicity to B-16 is mediated by the interacting semsitized thymus-derived (T) lymphocytes and macrophages (Mchi) or adherent cells. Separation of immune SC or PC into their adherent and nonadherent components, depletion of the adnerent cells or elimination of the theata-bearing cells from an enriched T cell population all result in the abrogation of cytotoxicity, whereas, recombination of T cells and Mchi re-establishes this effect. Three modes of Mchi/T cell interactions occur: 1) LM immune peritoneal or splenic T cells interact or synergize with their respective adherent cells to become cytotoxic to B-16; 2) combination of peritoneal Mchi and splenic T cells are noncollaborative and therefore noncytotoxic; 3) the cooperative effect of spleen T cells with Mchi are suppressed or inhibited by addition of peritoneal Mchi. Splenic Mchi, however, are neither uncooperative nor inhibitory when interacting with peritoneal T cells. Normal adherent cells can substitute for immune cells in all the cell-cell interactions with similar end results. These results demonstrate that specifically sensitized T cells interact with Mchi for expression of LM-induced nonspecific tumor cell destruction in vitro, however, such interactions may also be noncooperative or suppressive, thus resulting in tumor cell proliferation.