Various studies have shown that peritoneal dialysis patients may require less erythropoietin (rHuEPO) than maintenance hemodialysis patients. Iron deficiency in hemodialysis patients may contribute to the difference in response. This study compares the response to rHuEPO in 24 patients on CAPD to 33 patients on hemodialysis. All the hemodialysis patients received intravenous iron to prevent iron deficiency. Peritoneal dialysis patients received rHuEPO subcutaneously twice weekly. Erythropoietin was administered intravenously thrice weekly in hemodialysis patients. In peritoneal dialysis patients, hematocrit was 23.1% and 30.1%, rHuEPO dose was 80.9 and 89.0 u/kg/wk, while in hemodialysis patients hematocrit was 22.2% and 31.2%, and rHuEPO dosage was 140.2 and 154.3 u/kg/wk at initiation, and six months after therapy (p < 0.05 for dose, hemodialysis vs CAPD). Serum iron and transferrin saturation remained normal both in peritoneal and hemodialysis patients. These findings suggest that hemodialysis patients require a higher dosage of rHuEPO than peritoneal dialysis patients for a comparable rise in hematocrit, even when iron deficiency is prevented with parenteral iron. The improved efficacy of rHuEPO in CAPD patients may be due to the better removal of the inhibitors of erythropoiesis and/or the subcutaneous route of administration.