Antibody-dependent cell-mediated cytotoxicity in the Moloney sarcoma virus (MSV) system was evaluated in terms of the differential ability of IgG and IgM from MSV regressor animals to induce cytotoxicity by lymphocytes from lymph node, spleen, and thymus. The cell-mediated cytotoxicity induced by both IgM and IgG was specific for target possessing the appropriate virally determined cell surface antigen(s). IgM induced cytotoxicity by lymphocytes from all the organs tested. However, differences in magnitude and efficiency were revealed. Lymph node cells and thymocytes were most efficient against IgM-coated target cells. Against IgG-sensitized target cells, spleen and lymph node cells were about equally active, but thymocytes were inactive. Cortisone treatment of the donors of effector cells revealed that the cortisone resistant subpopulation of thymocytes, 2 days after cortisone injection, exhibited an increased cytotoxicity against target cells treated with unfractionated antiserum and its IgM fraction. This subpopulation of thymocytes was also cytotoxic against IgG-coated target cells. At 12 days after cortisone injection, the repopulated thymus showed little change in activity, compared to control thymus, against antibody-coated target cells.