TGF-β signaling is mediated through two types of serine/threonin kinase-containing receptors, type I (TGF-βRI) and type II (TGF-βRII), which form a heteromeric complex. In this signaling complex, ligand binding TGF-βRII phosphorylates and thereby activates the TGF-βRI to signal downstream pathways. To determine the role of TGF-βRII in embryogenesis, we have generated a TGF-βRII gene (Tgfbr2) knockout mouse line. The heterozygousTgfbr2knockout mice are developmentally normal. The homozygousTgfbr2mutation causes defects in the yolk sac hematopoiesis and vasculogenesis, resulting in an embryonic lethality around 10.5 days of gestation. This phenotype is indistinguishable from the previously reported embryonic lethality by the homozygous TGF-β1 gene (Tgfb1) null mutation. In addition, we have generated chimeric mice using aTgfbr2(−/−) embryonic stem cell line. Some chimeric mice showed several types of congenital anomalies, suggesting that TGF-βRII is important for normal development in a variety of organs.