Erythropoiesis was stimulated in 2- to 5-day-old normal neonatal rats nursed by phlebotomized mothers, and in 12-day-old hypertransfused neonatal suckled for 4 days by a twice-bled mother. Erythropoietic stimulation was evidenced as increases in hemoglobin levels and numbers of peripheral reticulocytes in the 2- to 5-day-olds, and by a higher 48-hour RBC-59Fe incorporation in the hypertransfused than in control 12-day-olds. The reticulocyte maturation curve was shifted to the left in 14-day-old transfused rats suckled by an anemic mother, in 14-day-old normal rats suckled by an anemic mother, and in 12-day-old transfused neonates fed cow milk to which erythropoietin (Ep) had been added. The oral administration of cow milk containing Ep to 10-day-old normal neonates induced a reticulocytosis. One-day-old rats suckled by mothers bled 72 h prior to delivery exhibited significant amounts of Ep in their plasma as compared to nondetectable levels in 1-day-old control rats of normal mothers. Decreases in relative percentages of nucleated erythrocytes were noted in spleens of hypertransfused 12-day-old neonates nursed by anemic mothers, in spleens of hypertransfused 12-day-old injected with Ep, and in spleens of 14-day-old normal rats suckled by an anemic mother. Nucleated erythrocyte numbers were reduced in both spleen and marrow of 12-day-old anemic neonates. The data suggest that: Ep is transmitted to neonatal rats via maternal milk, and in the process of gastrointestinal tract absorption, escapes inactivation, thereby stimulating erythropoiesis in these animals; Ep acts on already differentiated erythroid cells by influencing their rate of maturation.