Premature infants < 1500 g were randomly assigned to study and control groups. In the study group, 42 premature infants received recombinant human erythropoietin (r-Hu EPO) 750 U/kg per week subcutaneously from day 5 to 40 and enteral iron supplementation of 2 to 6 mg/kg/d beginning on day 14 provided that they were receiving at least 50% energy intake orally. In the control group, 51 infants received the same dose of enteral. iron supplementation beginning at the end of the fourth week. At the end of a 12-week monitoring period, r-Hu EPO combined with early enteral iron reduced transfusion needs only in the subgroup < 1000 g. r-Hu EPO and early iron treatment had no effect on the development of severe retinopathy of prematurity, intraventricular hemorrhage, necrotizing enterocolitis, and bronchopulmonary dysplasia. We suggest that r-Hu EPO combined with early enteral iron is both effective and safe in infants < 1000 g.