Although cortical thymocytes were found to be the predominant ecotropic and MCF-virus producers in the thymus of leukemia prone AKR mice the initial ecotropic retrovirus producing cells have been detected among a low density subpopulation of thymocytes including both PNA(+) and PNA(-) cells. Leukemosuppressive anti-viral treatment of these animals results in several important changes in the AKR thymus, including the elimination of virus producing cells, the induction of cellular phenotypic alterations, a decreased ability to bind ecotropic and MCF virus, a resistance to challenge with leukemogenic exogenous retroviruses, and the apparent elimination of a population of virus producing radioresistant cells. In addition, complement-mediated depletion with anti-viral IgG resulted in the complete elimination of proliferating thymocytes. These results suggest that passive anti-viral immunotherapy effectively eliminates a population of thymocytes which serve as the neonatal source of endogenous retroviruses and interferes with the earliest stages of leukemogenesis in AKR mice.