The alpha 2 beta 1 integrin serves as a receptor for collagens, laminin, and several other nonmatrix ligands. Many studies have suggested that the alpha 2 beta 1 integrin is a critical mediator of platelet adhesion to collagen within the vessel wall after vascular injury and that the interactions of the platelet alpha 2 beta 1 integrin with subendothelial collagen after vascular injury are required for proper hemostasis. We have used the alpha 2 beta 1 integrin-deficient mouse to evaluate the contributions of the alpha 2 beta 1 integrin in 2 in vivo models of thrombosis. Studies using a model of endothelial injury to the carotid artery reveal that the alpha 2 beta 1 integrin plays a critical role in vascular thrombosis at the blood-vessel wall interface under flow conditions. In contrast, the alpha 2 beta 1 integrin is not required for the formation of thrombi and pulmonary emboli following intravascular injection of collagen. Our results are the first to document a critical in vivo role for the alpha 2 beta 1 integrin in thrombus formation at the vessel wall under conditions of shear following vascular injury.