Atherosclerotic plaque with central depression (depressed lesion) may indicate regression of atherosclerosis in the aorta. Aortic depressed lesions have a solitary elevated area of plaque with a sharply-bordered roung depression in its center and no area ulceration. This may be interpretable as a sign of regression of atherosclerosis. To clarify the pathogenesis of depressed lesion, we studied clinical risk factors such as hypercholesterolemia in patients with depressed lesions that were confirmed at autopsy. The patients were divided into 3 groups according to their total cholesterol level at autopsy: a high-risk group (> or = 220 mg/dl), a moderate-risk group (180-220 mg/dl), and a low-risk group (< or = 180 mg/dl). Depressed lesions were found in 16.4% of those in the high-risk group, in 14.6% of those in the moderate-risk group and in 69.0% of those in the low-risk group. Severe aortic atherosclerosis was found in 69.8% of the patients; 50.9% of those with severe disease were in the-low risk group. Depressed lesions were also found in those with low levels of low-density lipoprotein cholesterol (< or = 140 mg/dl), 58.8% of whom were found to have severe atherosclerosis. There was no relationship between total cholesterol level and the presence of depressed lesions. However, a clinical prevention trial may result in sufficient control of ahterosclerosis among those in the high-risk group and may also lead to regression of aortic lesions.