We characterized several aspects of spontaneous regression of lymphocytic leukemia in mice. The disease, induced by the helper murine leukemia virus (MuLV) component obtained from the regressing Friend virus complex (RFV), was characterized by spleen and lymph node enlargement, thymus involvement, and anemia. Leukemia regression occurred in about 25% of infected mice and resulted in the return of lymphoid organs to near-normal weight and normal histology and the recovery from anemia. A tenfold to 1,000-fold decrease in virus titer was seen in those mice in which leukemia regressed when compared to leukemic animals, although infectious virus was still recoverable from apparently normal spleens. The sera of mice in which leukemia regressed contained potent virus-neutralizing activity that was associated mainly with immunoglobulins. These studies firmly supported the evidence that the regressing phenotype of RFV was due to its helper MuLV component (MuLV-RF).