An 80-year-old man with chronic renal failure (CRF) had pure red cell aplasia (PRCA) 9 months after starting the subcutaneous administration of recombinant human erythropoietin alfa (rHuEPO-alpha). Owing to the advanced renal failure, conventional immunosuppressive therapies were not practicable. It was decided to administer rituximab (4 cycles of 375 mg/m2/wk). PRCA was treated successfully with rituximab. The administration of rHuEPO-alpha then was resumed via the intravenous route with a satisfactory correction of anemia (12 months after the EPO-alpha rechallenge the patient is still transfusion independent). To the authors' knowledge, this is the first report of (1) a successful treatment with rituximab with CD20 depletion in a CRF patient with PRCA and (2) a successful intravenous resumption of the same rHuEPO-alpha.