Immune responses were examined after immunization with chicken erythrocytes (CRBC) in mice. Cytotoxicity of spleen cells was assessed by the release of 51Cr from labelled target cells. (1) At early stages (day 4-7) after primary intraperitoneal immunization, direct cytotoxicity of spleen cells was raised efficiently in C57BL/6 and AKR mice, but not in C3H/He, SL and DDD mice. Delayed hypersensitivity and antibody production were raised to almost the same extent in all the strains at such periods. (2) Effector cells in direct cytotoxicity were theta-positive and IgG-positive, and glass-nonadherent and Nylon wool column-adherent. Effector cells in antibody-dependent cell-mediated cytotoxicity in the presence of antibody to CRBC were eliminated by treatment with anti-IgG serum, but not by treatment with anti-theta serum. (3) Cytotoxicity and antibody production were raised efficiently after intraperitoneal or intravenous immunization, but not after footpad immunization. On the other hand, delayed hypersensitivity developed most efficiently after footpad immunization.