Recombinant human erythropoietin (rHuEPO) induced antibody-mediated pure red cell aplasia (PRCA) was a rare disease. Herein, we reported 2 cases with confirmed diagnosis of EPO- induced antibody-mediated PRCA in our institution. Case 1: a 53 year-old female with uremia and regular hemodialysis was regularly administered with EPO-α (Eprex) subcutaneously. Progressive unexplained anemia was noted 13 months after therapy with Eprex. Bone marrow study revealed remarkable erythroid hypoplasia compatible with PRCA. Anti-EPO antibody levels were detected. After withdrawal of Eprex and administration of cyclosporine, her anemia gradually improved. Serum level of anti-EPO antibody became undetectable. Another form of EPO (darbepoetin) was administered to the patient and hemoglobin recovered to 10.4 g/dL. Case 2: a 46 year-old male with chronic kidney disease related anemia underwent a regular subcutaneous EPO-β (Recormon) therapy. He developed profound anemia in spite of dose increase of EPO-β and combination with darbepoetin usage. EPO induced antibody-mediated PRCA was confirmed by the detection of anti-EPO antibody and severe erythroid hypoplasia in the bone marrow. Cessation of EPO and initiation of immunosuppression therapy with methylprednisolone and azathioprine were instituted. The patient finally became transfusion-independent.