AKR/J mice, 80-90% of which ordinarily die of spontaneous lymphocytic leukemias by 12 months of age, were significantly protected from developing leukemia in the initial experiment by a single course of treatment with AKR serotype-specific antibodies mad in goats and processed as immune gamma globulin (IgG). In experiment 1, IgG was given on the day of birth and on four additional days, and finished on day 14. This schedule resulted in suppression of over 4 logarithms of normal virogene expressions up to 25 days of age and led to partial viral suppression for over 200 days of age. At 365 days of age, 20 of 24 (83.3%) control animals were dead of leukemia whereas six of 30 (20%) treated animals had died of leukemia. In a second experiment, only four inoculations of IgG were given from birth to 20 days, after which they were given three inoculations of radiation-killed vaccine specific for AKR-Gross leukemia virus and one injection of murine sarcoma virus-Gross leukemia virus 10 days later. This combined immunization procedure provided significant virus suppression up to 288 days of age. At 300 days of age, 30 of the 50 (60%) controls had died of leukemia while only 1 of 24 (4.2%) of the immunized mice developed fatal leukemia; the significance of protection for each of the experiments was P LESS THAN 0.001. We conclude that these data establish in classical fashion with type-specific immunosuppression the determining role of type-C endogenous virogenes in leukemogenesis and, at the same time, also established the feasibility of nearly total prevention of leukemia in AKR mice.