Cellular proliferation in response to endothelial injury has been examined extensively in experimental animals. Under certain conditions (e.g., hypercholesterolemia and hypertension), this response can be exaggerated and develop into lesions that resemble early atherosclerosis. The injury caused by endarterectomy in human beings and the repair of the arterial wall that ensues may be analogous to the animal models. Presumably, those patients with an exaggerated proliferative response manifest myointimal hyperplasia and recurrent stenosis. To determine potential causes of recurrent stenosis after carotid endarterectomy, we studied 31 patients with early restenosis (group I), 35 patients with later restenosis (group II), and compared them with a control group of 100 consecutive patients who underwent uncomplicated carotid endarterectomy (group III). The known risk factors for atherosclerosis were analyzed. There was no significant difference in the male-to-female ratio, number of cigarettes smoked, or incidence of diabetes mellitus. However, the serum cholesterol level for group I was 282 +/- 57 mg/dl (p less than 0.001 versus controls) while the serum cholesterol level in group II was not significantly elevated over that of the control group. Both groups I and II had a higher incidence of hypertension (p less than 0.005 for both versus controls). There were no differences in the severity of hypertension. The data suggest that hypercholesterolemia has a strong association with early restenosis after carotid endarterectomy but not with late recurrent disease and that hypertension, even when treated, may be associated with both early and late recurrent stenosis.