To determine the natural history of changes in plaque morphology and luminal diameter of atherosclerotic carotid arteries, we used duplex scanning to follow-up (1) the contralateral artery in 289 patients who had undergone carotid endarterectomy, with a mean follow-up 22 months and a range of 0 to 48 months and (2) the carotid arteries in 130 patients who had no surgical treatment and had been symptom free, with a mean follow-up period of 15 months and a range of 0 to 48 months. Plaques were graded as to the ratio of echolucency to echogenicity, with type 1 being most echolucent and type 4 being most echogenic. A normal-appearing artery was classified as type 5. Heterogeneous plaques (types 1 and 2) occurred significantly more (p less than 0.001) in symptomatic preoperative arteries than in asympatomatic arteries. Follow-up of the asymptomatic vessels showed that the majority of plaques either remained the same or became more echogenic (fibrous). Approximately one fourth of plaques in each group degenerated (more echolucent). Thirty-one patients (10.7%) developed new symptoms in the contralateral asymptomatic group, with 10 patients (3.5%) having strokes. Fourteen of 130 (10.8%) patients, or 5.4% of vessel territories at risk, in the primary asymptomatic group developed new symptoms, with only two strokes occurring. In the contralateral asymptomatic group those patients who initially had greater than 75% stenoses fared worse than those with primary asymptomatic disease with greater than 75% stenosis. Although the overall development of new symptoms is low in both populations, our data indicate that those patients with heterogeneous plaques or whose plaques have undergone change may be at risk for new symptoms. Longer follow-up studies are needed to define the role of plaque changes in the development of symptoms. For now we advocate a conservative "wait and see" approach to symptom-free patients with greater than 75% stenoses and calcified plaques. We suggest a more aggressive approach, recommending early surgical intervention, to those few patients with heterogeneous plaques.