Mononuclear phagocytes: a major population of effector cells responsible for rejection of allografted tumor cells in mice. To understand the in situ mechanism of immunological response of recipient animals to allografted tumor cells, the types of cells that infiltrated into the rejection site were examined. When Meth A cells (H-2d) were given i.p. to an allogeneic [C57BL/6 (H-2b)] strain of mouse, the tumor cells ceased to grow on the 6th day, accompanied by an i.p. infiltration of leukocytes. The tumor cells were totally eliminated from the peritoneal cavity around the 12th day. The highest cytotoxic activity against Meth A cells was obtained with the peritoneal exudate cells harvested on day 8. On this day, the exudate cells consisted of three populations when examined by flow cytometry, and each was isolated by sorting. Each of them appeared to be homogeneous, and they were morphologically identified as lymphocytes; granulocytes; and medium-sized, mononuclear, less-granular cells. The cytotoxic activity was confined exclusively to the last population. The effector cells (H-2b) were cytotoxic against not only Meth A cells (H-2d) but also concanavalin A-stimulated allogeneic spleen cells [C3H/He (H-2k), CBA/N (H-2k), A/J (H-2a), BALB/c (H-2d), and DBA/2 (H-2d) strains of mouse]. The effector cells were totally inert against concanavalin A-activated syngeneic spleen cells [C57BL/6 (H-2b) and C57BL/10 (H-2b) strains of mouse]. The effector cells were phenotypically (Thy-1.2- CD3- Lyt-1- Lyt-2- L3T4- immunoglobulin- asialo GM1-), morphologically, and functionally distinct from cytotoxic T cells, natural killer cells, and lymphokine-activated killer cells but were adherent mononuclear phagocytes. 