The α integrin GPIIb is a marker of hematopoietic progenitors. Using a marking strategy based on Cre-loxP technology to trace the fate of GPIIb-expressing cells, we show that GPIIb is expressed during early definitive embryonic hematopoiesis. However, the marked fetal population is distinct from the hematopoietic cells that predominate in the adult, suggesting that at least two waves of progenitors arise concurrently or consecutively in the fetus. Furthermore, using an inactivated allele of gpIIb, we provide evidence for a functional role of GPIIb on progenitors. We observe an increase in hematopoietic progenitors in the yolk sac, fetal liver, and bone marrow, an effect which may, in part, be explained by loss of binding to fibronectin.