While renal anemia can be successfully treated by use of erythropoietin (EPO) in most hemodialysis (HD) patients, some patients have anemia that is refractory to treatment with a high dose of EPO. We examined whether L-carnitine treatment could raise hematocrit (Hct) levels in such patients. Fourteen HD patients who showed a poor response to EPO and no evident factors which inhibit a response to EPO were selected to receive oral L-carnitine (500 mg/day) in a 3-month trial. During the study, 36% of the patients showed Hct increases of more than 2%. Statistical analysis revealed significant increases of Hct (p = 0.003) and total iron-binding capacity (TIBC) (p = 0.050) and a significant decrease of ferritin (p = 0.005). In addition, we found that red blood cells (RBCs) in HD patients contained a comparable level of carnitine to normal controls, despite the presence of serum carnitine deficiency, and that RBC carnitine was not removed through HD, in contrast to serum carnitine. These results suggest that RBC carnitine may be essential for RBCs to perform their metabolic function in renal anemia and that oral L-carnitine treatment could improve anemia in poor responders to EPO.