In six preterm infants we tested the hypothesis that, as is the case in infant rats, orally administered recombinant erythropoietin (EPO) would be absorbed and would stimulate erythropoiesis. Three study subjects were younger than 1 week old and had never been fed and three were more than 1 month old and were receiving enteral feedings totally. Two hours after the administration of large doses of EPO (1000 U/kg body weight) only a small increase in serum EPO concentrations (from 6.3 +/- 0.9 to 13.3 +/- 2.8 mU/ml, mean +/- SEM) was observed. No further increases were observed 4, 6, 12, or 24 hours after the administration. No increases in reticulocyte count or hematocrit were observed after 10 days of EPO administration. We conclude that, unlike the situation in infant rats, enterally administered recombinant EPO is not absorbed in significant amounts by human preterm infants. Therefore oral administration will not be an effective substitute for subcutaneous or intravenous EPO administration in preterm infants.