The blood of the newborn horse was found to have a higher affinity for oxygen than that of the mother. This difference was due to the fact that the red cells of newborn foals contained 36% lower 2,3-diphosphoglycerate (2,3-DPG) than red cells from their respective mares. The ATP levels of foal and maternal red cells did not differ significantly. Following birth a prompt rise in the foal's red cell 2,3-DPG occurred, approaching normal (maternal) levels within 5 days. Unlike many other species, the hemoglobins of the newborn and adult horse have been shown to be structurally identical. Furthermore, phosphate-free solutions of newborn and maternal hemoglobins had identical oxygen saturation curves in the absence and presence of added 2,3-DPG. This study demonstrates that, in contrast to other species. the increased oxygen affinity of horse fetal red cells is due to a lower level of the cofactor 2,3-DPG rather than to the presence of fetal hemoglobin.