Male Wistar rats were used in a study of removal of the endothelium and endothelial regeneration in the large arteries. The endothelium was stripped completely by surgery from a well-defined segment, with no branches, of the left common carotid artery of rats, drying the vessel by blowing a gentle air stream through the lumen. The animals were fed the normocholesterolic or hypercholesterolic diets. The conditions of the denuded arterial segment were checked histologically at various intervals after the operation. The exposed area became covered with new endothelial cells growing from the two margins of the damaged area; regeneration was complete by about 20 days in normocholesterollemic rats (99.06%) and in a slightly lower proportion of the rats on the atherogenic diet (90.56%). The animals with induced hypercholesterolemia, however, had a significantly larger amount of missing endothelium on day 11 after surgery than the controls. This suggests that hypercholesterolemia affects not only the severity of the lesion but also the rate of endothelial repair.