Antibody-dependent, cell-mediated cytotoxicity in the Moloney sarcoma virus (MSV) system was analyzed in terms of the ability of autochthonous antibody to induce or potentiate cytotoxicity by lymphocytes from animals infected with MSV. As previously demonstrated in microcytotoxicity assays, the lymphocytes from regressor animals taken 30 days after virus infection were consistently more cytotoxic than those from tumor-bearing animals 15 days after infection. Antisera from the regressors potentiated the activity of regressor lymphocytes from the same animals. Also, antisera from tumor bearers, 15 days after virus injection, induced cytotoxicity by the animals' autochthonous lymphocytes which, by themselves, were not cytotoxic. In an independent assay for antibody, both groups of sera produced cytotoxicity by control nonimmune lymphocytes. Specificity controls indicated that both antibody and lymphocytes were required for the induction of cytotoxicity against the target cells in vitro. Normal sera placed on the target cells in the same concentrations induced no cytotoxicity by the immune lymphocytes, and immune sera alone placed on the target cells caused no cytotoxicity. The cooperative activity between antibody and lymphocytes may be a factor that accounts for the observed high incidence of spontaneous tumor regression.