Iron deficiency is an important factor for high erythropoietin (EPO) requirements. Some studies have shown a decrease in recombinant human erythropoietin (rHuEPO) dosage with correction of iron deficiency. This is a 2 year prospective study of 58 chronic hemodialysis (HD) patients in whom iron deficiency was corrected with intravenous iron therapy. Patients were stratified into two groups: Group 1 with 25 patients (EPO < 70 U/kg per HD), and Group 2 with 33 patients (EPO > 70 U/kg per HD). For Groups 1 and 2, respectively, differences in mean age (56.5 vs 64.1 years), rHuEPO dose (30.1 vs 148.7 U/kg per HD), and hematocrit concentration (36.5% vs 32.7%) were statistically significant (p < 0.05). Although iron saturation was 45% compared with 41.3% for Groups 1 and 2, respectively, serum parathyroid hormone, aluminum, and urea reduction ratio were similar for both. These data suggest that some patients continue to require a high rHuEPO dose in spite of adequate iron repletion. Further investigation into factors causing EPO resistance is important to decrease rHuEPO requirements and improve cost effectiveness.