Thickness of carotid artery atherosclerotic plaque and ischemic risk. Noninvasive duplex scanning of carotid artery atherosclerotic plaque was performed in 286 consecutive patients referred to a cerebrovascular diagnostic laboratory. The presence and thickness of such plaque in the region of the carotid bifurcation were examined for association with the degree of vessel stenosis, age, sex, smoking history, history of prior transient ischemic attack or stroke, and systemic manifestations of atherosclerotic disease. Atherosclerotic plaque thickness was positively correlated with degree of vessel stenosis (P less than 0.0001). Both parameters were independent predictors of cerebrovascular events but plaque thickness was a better predictor of prior transient ischemic attacks (P less than 0.05), and vessel stenosis was a better predictor of prior stroke (P less than 0.005). Patient age (P less than 0.001) and pack-years of cigarette use (P less than 0.001) were independent positive predictors of carotid atherosclerotic plaque thickness. The greatest effect of smoking and atherosclerotic plaque thickness was seen in heavy smokers younger than age 55. Both carotid artery plaque thickness and pack-years of smoking were significant independent predictors of other systemic manifestations of atherosclerotic disease (P less than 0.05). Such noninvasive scanning of carotid artery atherosclerotic plaque demonstrates the significant role of age and smoking in the progression of disease. It also suggests a significant role for carotid atherosclerotic artery plaque in the pathophysiology of cerebrovascular events, especially transient ischemic attacks, even prior to the production of a flow-limiting stenosis. Finally, noninvasive screening of carotid artery plaque may provide a useful marker for the patient at risk for systemic atherosclerotic disease and identify the patient for whom maximal atherosclerotic risk factor modification is needed. 