Recombinant human erythropoietin (rhEpo) has proved to be remarkably safe and effective for the treatment of anemia. Despite the use of rhEpo, concerns about its cost, the need for frequent parenteral administration, and the development of anti-Epo antibodies have prompted the development of improved agents to rescue anemia. Patients with anemia associated with renal disease are usually treated by intravenous or subcutaneous rhEpo administration; however, some patients do not respond well to rhEpo, because of the presence of Epo antibody or other unknown reasons. A new, orally administered drug is needed as an economical and effective method to treat such patients. We administered 1.3 g/day of L-arginine to 8 elderly patients with anemia associated with renal disease. All 8 patients responded to the treatment with increases in hemoglobin levels. Six of the patients showed improved renal function. There were no significant adverse effects. Our data show that oral administration of 1.3 g/day of L-arginine significantly improves Epo production and reverses anemia without adverse effects in elderly patients who have anemia associated with renal disease and are in the predialysis state of chronic renal failure.