TISSUE factor, a member of the cytokine-receptor superfamily and high-affinity receptor and cofactor for plasma factor Vll/VIIa (ref. 1), is the primary cellular initiator of blood coagulation. It is involved in thrombosis and inflammation associated with sepsis, atherosclerosis and cancer², and can participate in other cellular processes including intracellular signalling³, metastasis⁴, tumour-associated angiogenesis⁵, and embryogenesis⁶. Here we report that inactivation of the tissue factor gene (TF) results in abnormal circulation from yolk sac to embryo beyond embryonic day 8.5, leading to embryo wasting and death. Vitelline vessels from null mice were deficient in smooth-muscle α-actin-expres-sing mesenchymal cells, which participate in organization of the vessel wall. This implies that tissue factor has a role in bloodvessel development.