Cell-mediated immunity, using a xenogeneic system, i.e., mouse spleen cells attacking chicken erythrocytes (CRBC) is studied. In this system target cell lysis by spleen cells from immunized animals is complement independent, hence cell-mediated. It is specific because trinitrophenyl-(TNP) sensitized spleens lyse TNP-CRBC but not CRBC. CRBC-sensitized thymus-derived (T) lymphocytes cooperate with bone marrow-derived lymphocytes in induction of CRBC plaque-forming cells but cannot lyse CRBC as target. However, anti-CRBC antibody at concentrations too low to be detected by complement dependent lysis do induce cytotoxicity to CRBC in spleen cell suspensions containing T cells as well as in spleen cell suspensions depleted of T cells. Anti-ϑ serum absorbed to remove non-anti-ϑ antibody does not abrogate the cytotoxicity of immune spleen cells. These results indicate that the effector cell in this system is not a ϑ-antigen-bearing T lymphocyte. The effector cell is abundant in spleen and in the peritoneal cavity but not in lymph nodes of normal animals: it is bone marrow-derived, radiation resistant, and sticks to siliconized glass bead columns. Since, in addition, the effector cell can be separated from other spleen cells by treatment with carbonyl iron powder and a magnet, it is, we suggest, a phagocytic cell.