In a prospective study 376 carotid artery plaques (275 symptomatic, 101 asymptomatic) were obtained from endarterectomies (184 unilateral and 96 bilateral) in 280 patients. The gross morphologic features of each plaque were noted at surgery and, together with the patient's clinical history, stored in computer memory. These data were analyzed in order to investigate the relationship of gross morphologic plaque characteristics with both the presence of cerebral symptoms and the degree of stenosis associated with the plaque. Ulceration was the most frequently observed of the five major gross plaque morphologic characteristics (46.0% of all plaques), but only intramural hemorrhage (30.6% of all plaques) was significantly more common in all symptomatic compared with all asymptomatic plaques (p less than 0.02). Hemorrhage was also the only gross characteristic significantly more common in focal symptomatic plaques when compared with either asymptomatic plaques (p less than 0.05) or nonfocal symptomatic plaques (p less than 0.01). When all the plaques were divided into three broad degrees of stenosis groups (0-39%, 40-69%, 70-99%) on the basis of angiographic data, only hemorrhage showed a significant correlation in incidence with increased degree of plaque stenosis, both when all plaques were considered (p less than 0.001) and when only symptomatic plaques were examined (p less than 0.001). The results indicate that intramural hemorrhage is the only carotid plaque gross morphologic characteristic significantly more frequent in symptomatic compared with asymptomatic plaques and the only characteristic significantly correlated with increased plaque size. These findings indicate that factors other than plaque ulceration and intraluminal thrombus play an important role in carotid plaque related cerebral symptoms. The data also raise questions concerning the unequivocal value of anticoagulant therapy in carotid artery disease, especially in highly stenotic lesions.