Ep is the primary hormone responsible for erythrocyte production throughout development. It has been proposed that recombinant human Ep (rhEp) be used for the treatment of anemia in premature human neonates. Before doing so, it is important to examine pharmacokinetic parameters during development in animals. To do so we developed a sensitive and specific rhEp immunoprecipitation assay using polyclonal antisera. A non-compartmemai approach was employed to determine pharmacokinetic parameters in 6 fetal (FET) (125-133 d; 2.8-3.4 kg), 6 newborn (NB) (10-19 d; 5.0-10.6 kg), and 5 adult (ADULT) pregnant sheep (120-130 d gest) following bolus injection of tracer amounts of 125I-rhEp. Results (M ± SD) demonstrated more rapid plasma clearance (Cl), shorter terminal half-life (t1/2 beta), greater plasma distribution volume (Vd), and greater steady state distribution volume (Vss) in the FET and NB groups (Table). We speculate that low plasma Ep levels observed in premature newborn infants are not due to decreased Ep production, but instead are the result of rapid Ep elimination and large distribution volume. For rhEp to be effective in the treatment of anemia in premature neonates, it is likely that larger rhEp doses per kg than those used in Heating anemic adult patients will be needed.