Despite a large body of evidence showing the beneficial effects of successful treatment of anemia with recombinant human erythropoietin (EPO) in patients with end-stage renal disease, controversy remains as to whether EPO treatment of anemia can improve the nutritional status in patients on maintenance hemodialysis. This prompted us to conduct a prospective study in 41 hemodialysis patients with basal hemoglobin less than 9 g/dl. The dose of EPO was increased for 12 weeks to achieve the target hemoglobin concentration of 10 g/dl and then titrated in the following 12 weeks to maintain the target value. Nutritional status was assessed at baseline and after 6 months of follow-up, using the global protein-calorie malnutrition (PCM) index proposed by Bilbrey and Cohen. A low global PCM score indicates better nutrition. The results showed that hemoglobin values significantly increased from 8.7 +/- 0.8 g/dl at baseline to 10.7 +/- 0.5 g/dl in the 6th month (p < 0.001). No significant changes were observed in the normalized protein catabolic rate and Kt/V during the study period. Global PCM scores improved from 30.0 +/- 7.5 to 23.6 +/- 3.1 (p < 0.001) and paralleled the correction of anemia by EPO treatment. The data were consistent with a major improvement in the nutritional markers of relative body weight, triceps skinfold, midarm circumference, midarm muscle circumference, serum albumin, serum transferrin and total lymphocyte count in the 6th month as compared to baseline. The percentages of mild and moderate-severe PCM at baseline were 32 and 58%, respectively. These percentages were significantly reduced during the 6th month to 20 and 30%, respectively (p = 0.0004). In summary, correction of renal anemia with EPO improves the nutritional status in hemodialysis patients. A postulated mechanism is that EPO may exhibit anabolic effects, with a better utilization of ingested protein.