Heterotrimeric GTP-binding proteins (G proteins) participate in cellular signaling and regulate a variety of physiological processes. Disruption of the gene encoding the G protein subunit alpha(13) (G alpha(13)) in mice impaired the ability of endothelial cells to develop into an organized Vascular system, resulting in intrauterine death. In addition, G alpha(13) (-/-) embryonic fibroblasts showed greatly impaired migratory responses to thrombin. These results demonstrate that G alpha(13) participates in the regulation of cell movement in response to specific-ligands, as well as in developmental angiogenesis.