A teenage boy with mixed-cellularity Hodgkin disease presented with severe anemia secondary to pure red cell aplasia of marrow without evidence of lymphomatous infiltration or hemolysis. In vitro studies of the patient's serum demonstrated an inhibitor of erythropoietin activity which appeared to be an IgG but which did not directly bind erythropoietin. The patient's anemia resolved and the inhibitor disappeared following chemotherapy for Hodgkin disease. Presumably, the inhibitor was directed at a very early stage of red blood cell production. This phenomenon may be related to other autoimmune manifestations occasionally seen in patients with lymphomas. The case is presented to bring attention to the unusual occurrence of red cell aplasia in Hodgkin disease. Several hypotheses concerning significance and etiology of the anemia are detailed.