The spontaneous regression of a virus-induced murine leukemia was observed after inoculation of a particular strain of Friend leukemia virus. Mice inoculated with this strain exhibited an initial pathologic response identical to that induced by conventional strains of Friend virus. This was characterized by an intense proliferation of primitive cells of the splenic red pulp which led to massive splenomegaly by 21 days. This cellular response was accompanied by abundant virus proliferation. Unlike the fatal outcome produced by conventional virus strains, the leukemia induced by this strain appeared to be self-limiting. The extensive cellular proliferation diminished at 25–50 days, with a gradual return of the spleen to normal. At the same time, the abundant virus proliferation markedly decreased, as measured by infectivity, virion counts and focal lesions on the spleen. The capacity to induce the regressing form of erythroid leukemia was retained by this virus strain through 7 passages. The leukemia induced by 8 other strains of Friend virus maintained in our laboratory did not regress. Regression of leukemia was observed in various strains of Swiss and DBA/2 mice. In a 200-day survival study among mice whose leukemia was induced by conventional strains or the strain of virus causing a disease that regressed, a significant prolongation of life was observed in the mice receiving the latter virus strain.