Erythropoietin (EPO) induced a 42% increase in 3H-uridine incorporation into RNA after a 5-hr culture of normal bone marrow cell suspensions. Bone marrow cells obtained from rats 3-5 days after the initiation of a myelogenous leukemia exhibited a decreased responsivity to EPO. At this time incorporation of the isotope into RNA in the presence of EPO was approximately 50% of controls. Rats rendered leukemic 8-10 days prior to culture showed no bone marrow response to EPO even in those instances where leukemic cells comprised a relatively small percentage of the marrow compartment. EPO had little or no effect on RNA synthesis by spleen cells obtained from normal and leukemic rats. This was noted even in those leukemic spleens in which erythropoiesis was observed. The data suggest that the anemia associated with myelogenous leukemia may, in part, be due to a loss of EPO-responsive cells and/or a loss of sensitivity of these elements to normal humoral control.