We report on a 4-month-old Japanese infant girl with Diamond-Blackfan anemia (DBA) as shown by congenital macrocytic pure red cell hypoplasia with marked reduction of erythroid precursors in bone marrow, reticulocytopenia, increased fetal hemoglobin, and elevated adenosine deaminase activity in peripheral blood. She responded poorly to conventional doses of corticosteroids, however, with high-dose corticosteroids she responded with reticulocytosis and an elevation of hemoglobin level above 12 g/dL. Erythrophagocytosis was noted during the tapering period of prednisone when her hemoglobin level declined to 7.6 g/dL and reticulocyte level to 0.4%. At that time, the erythrophagocytosis was noted in about 60% of marrow histiocytes. These findings were not observed prior to or during the high dose prednisone therapy. We speculate that one of the causes of pure red cell aplasia and reticulocytopenia in DBA is mediated by erythrophagocytosis.