In 4 chronic hemodialysis patients we have tested whether the administration of reduced glutathione (GSH; Glutamed®, Boehringer Mannheim Italia; 1,200 mg i.v.) at the end of each hemodialytic session during 90 days could minimize oxidative damage to the red blood cells (RBC) and reduce the recombinant human erythropoietin requirements. Treatment with GSH was followed by an increase in RBC GSH content (n = 3), a normalization of the ascorbine cyanide test (n = 4), an increase in RBC survival (n = 3), and a reduction in 2 patients of the erythropoietin need (41 and 26%, respectively, after 3 months of therapy). When the GSH supplements were terminated, we noticed after 3 months a re-establishment of the baseline values. On the other hand, malonyldialdehyde, RBC deformability, and RBC splenic pool were abnormal before and remain abnormal during the test period. Since no adverse reactions were noticed, these findings seem to indicate that GSH could ameliorate the intraerythrocytic oxidative defense and could be as useful drug in the treatment of anemia in patients affected by chronic renal failure.