The event or mechanism that causes an asymptomatic atherosclerotic carotid artery to become symptomatic remains uncertain. Analysis of carotid endarterectomy surgical specimens from symptomatic patients has suggested that primary intraplaque hemorrhage is the most important initiating event. Reanalysis of several recent series of carotid endarterectomy specimens demonstrated that plaque disruption (ulceration) occurs as frequently as plaque hemorrhage, and that both processes are significantly more frequent in symptomatic as compared with asymptomatic endarterectomy specimens. A review of the coronary artery pathology literature reveals that plaque disruption is commonly present in patients with acute fatal myocardial infarction. It is widely asserted that coronary artery plaque disruption leads to luminal thrombosis and intraplaque hemorrhage. A similar sequence of events may occur in symptomatic carotid arteries.