Platelet endothelial cell adhesion molecule-1 (PECAM-1) (CD31) is an adhesion molecule expressed on endothelial cells and subsets of leukocytes. Analysis of phenotypically defined hematopoietic stem cells (HSCs) from the yolk sac, fetal liver, and adult bone marrow demonstrates CD31 expression on these cells throughout development. CD31⁺ c-kit⁺ cells, but not CD31^– c-kit⁺ cells, isolated from day-9.5 yolk sac give rise to multilineage hematopoiesis in vivo. Further evaluation of the CD31⁺ lineage marker–negative fraction of adult bone marrow reveals functionally distinct cell subsets. Transplantation of CD31⁺ Lin^– c-kit^– cells fails to protect lethally irradiated recipients, while CD31⁺ Lin^– c-kit⁺ Sca-1^– cells (CD31⁺ Sca-1^–) provide radioprotection in the absence of long-term donor-derived hematopoiesis. Although donor-derived leukocytes were not detected in CD31⁺ Sca-1^– recipients, donor-derived erythroid cells were transiently produced during the initial phases of bone marrow recovery. These results demonstrate CD31 expression on hematopoietic stem cells throughout ontogeny and identify a population of CD31⁺ short-term erythroid progenitors cells that confer protection from lethal doses of radiation.