Acquired pure red-cell aplasia (PRCA) is characterized by isolated severe anemia and reticulocytopenia (1) and by absent or markedly diminished erythroid precursors in the bone marrow, which is otherwise normal. It is associated with many disorders, including parvovirus B19 infection (2), lymphoproliferative disorders (3–4) rheumatologic diseases (5), thymoma (6), and (rarely) erythropoietin administration due to antierythropoietin antibody formation (7). Most cases of PRCA are idiopathic. With the exception of parvovirus infection (8), which responds to intravenous immunoglobulin, PRCA seems to have an autoimmune pathophysiology. Antibodies directed against early erythroid precursor cells (9–10) and cytotoxic T cells with specificity for erythroid progenitors (11) have been described. In early studies in a patient with T-cell large granular lymphocytic leukemia, malignant T lymphocytes inhibited erythroid colony formation (12), which was reversed in vitro by antithymocyte globulin and complement. Immune-mediated PRCA shares many clinical associations and pathophysiologic mechanisms with aplastic anemia. In PRCA associated with thymoma, a thymectomy may produce responses in as many as 40% of patients (13). Plasmapheresis has successfully treated PRCA associated with systemic lupus erythematosus and after major ABO-mismatched bone marrow transplantation (14). Various immunosuppressive treatments have been reported as effective, such as corticosteroids, splenectomy (15), thymectomy (16), cyclophosphamide (17–18), and azathioprine (19). Corticosteroids produce responses in about 50% of patients (20), but long-term use is associated with clinically significant morbidity. Patients have responded to treatments for large granular lymphocytic leukemia, as well as cyclosporine alone. In PRCA associated with large granular lymphocytic leukemia, 28 of 47 patients treated with cyclosporine (21) had a hematologic response that may reflect the responsiveness of the underlying disorder to cyclosporine. Of 9 steroid-refractory patients, 6 patients (66%) responded to antithymocyte globulin (22). Less toxic but equally effective therapeutic strategies could avoid the need for hospitalization (required for antithymocyte globulin) and monitoring of drug levels (required for cyclosporine) and avoid potentially serious collateral organ damage (seen with long-term use of corticosteroids). Recently, responses to the anti-CD20 monoclonal antibody (rituximab) (23–24) have been reported in patients with chronic lymphocytic leukemia and in PRCA associated with erythropoietin use. In both cases, PRCA has been attributed to antibodies against erythroid precursors.