Thrombus formation at a ruptured arterial plaque forming a stenotic luminal outgrowth may trigger acute vascular occlusion. The pathobiology of the complex mechanisms and their interrelationships during this event is not fully understood. However, it is generally believed that components of the subendothelial plaque and the disturbed blood flow conditions caused by the stenosis are of pivotal importance for the thrombus formation. The shape and the severity of the occluding stenosis have profound impacts on the physical aspects of the blood flow. The wall shear rate at the apex may reach extremely high values (> 40,000 s-1). Zones of recirculation proximal and distal to the stenosis as well as turbulent blood flow further downstream from the lesion may occur. The significance of these rheological factors for the mural thrombus formation at various locations at the stenosis is not well established. The extracellular matrix and the cellular components of the subendothelial plaque exposed to the blood stream following plaque rupture are potent inducers of thrombus formation. Matrix components such as collagen fibrils, fibronectin and von Willebrand factor interact specifically with platelet membrane glycoprotein receptors, Ia-IIa, Ib-IX, and IIB-IIa, enabling platelet-subendothelium adhesion, particularly at high wall shear rates. The coagulation cascade is concomitantly activated by the binding of FVII from plasma to tissue factor expressed on the membranes of macrophages and smooth muscle cells. Thrombin, which is subsequently generated at the rupture, enhances the platelet recruitment, and thus the thrombus growth. The thrombin formation simultaneously enhances the deposition of fibrin in and around the platelet masses. Further augmentation of these processes is mediated by the formation of prothrombinase complexes on the phospholipid-rich surfaces of the activated platelets, which increases the local concentration of thrombin at the evolving thrombus. Thrombus fragmentation may represent a serious event, since these fragments may embolize and occlude smaller vessels, producing ischaemia. It is apparent that acute arterial thrombotic occlusion triggered by a ruptured stenotic plaque involves both physical and chemical mechanisms. The inter-relationship and the significance of these complex mechanisms are not well understood. Efficient modalities for therapeutic intervention in thromboembolism at such lesions may not be available before the physical and chemical events are better identified and characterized.