In this case report we describe two patients with pure red cell aplasia (PRCA) as an initial manifestation of systemic lupus erythematosus (SLE). Antibodies to erythropoietin were determined, by an ELISA method developed in our laboratory, in frozen serum obtained from one of the patients. A high titer of antibodies to erythropoietin was detected in serum obtained before treatment with high dose intravenous immunoglobulin (IVIG). The antibody titer declined after successful treatment. This observation suggests that antibodies to erythropoietin may contribute to the pathogenesis of SLE associated PRCA.