The effect of recombinant human (r-Hu) erythropoietin (Epo) (300 IU/Kg per week for 4 weeks) was studied in healthy preterm infants (n = 14) fed human milk with additional milk protein and high doses of iron. The controls (n = 15) were in themselves a study group and were used to follow the natural course of anaemia of prematurity on such nutrition. Serum immunoreactive Epo (SiEpo) increased significantly 24 h after r-HuEpo injections (range 36 to > 128 mU/ml) and remained at these levels throughout the treatment period. r-HuEpo in such moderate doses kept haemoglobin above 11 g/dl. Bodyweight gain, protein and iron parameters indicated adequacy of dietary protein and iron. In controls, siEpo increased during the first weeks after nutritional supplementation, with a concommitant rise in reticulocyte count. At age 3 weeks, despite low siEpo levels, reticulocyte counts indicated active erythropoiesis. Following further moderate increases in siEpo, the reticulocyte count increased to high levels (7%). The reticulocyte response suggests that erythropoiesis in preterm infants is less dependent upon Epo levels than in adults.