A prominent manifestation of the prelymphoid leukemic phase of Rauscher virus infection is anemia. Mice given injections of high closes of virus showed a progressive anemia and died within 6–8 weeks after infection, whereas those infected with lower doses eventually stabilized their hemoglobin concentration and packed cell volume, but at lower than normal levels. The anemia initially was due to a combination of relative bone marrow failure and hemolysis, as indicated by a decreased red blood cell (RBC) survival. However, within 3–6 weeks the bone marrow recovered, as indicated by a return to normal of the59Fe reappearance and the development of reticulocytosis, but the hemolysis persisted. The anemia and severity of bone marrow suppression were potentiated by splenectomy. Rauscher virus infection caused increased osmotic fragility, autohemolysis, and adenosine triphosphate (ATP) instability of the RBC. The increased autohemolysis and ATP instability were prevented by the addition of glucose to the RBC suspensions. Young and old cells were equally susceptible to hemolysis. The data indicate that the shortened RBC survival was probably due to a direct effect of the virus on the RBC membrane. The altered crythropoiesis was a non-neoplastic manifestation of Rauscher virus infection.