A study was made of events occurring in the arterial wall of the rat after administration of an atherogenic calcification-inducing diet and of vascular response in a model of combined metabolic aggression (atherogenic, calcification-inducing diet) and surgical aggression (adventitial resection). Female Sprague-Dawley rats were fed an atherogenic, calcification-inducing diet for 24 consecutive days, after which half the rats returned to standard diet (group I, n = 12) and the other half (group II) underwent resection of the adventitia on a segment of common iliac artery on day 25 before returning to standard diet. Normolipemic rats and rats that underwent adventitial resection without the atherogenic, calcification-inducing diet were used as the control groups. The rats were killed at 10 min, 1 and 24 h, 5, 14, 21, 30, 50, 70, 120 and 180 days. Morphologic studies were made with light microscopy and electron microscopy (scanning and transmission), as well as biochemical studies. Monocyte adherence and infiltration of the arterial intima, thickening of the subintimal space, the presence of monocyte-macrophages, calcification in the medial layer, intense adventitial fibrosis, and vacuolization of the endothelial cells of the adventitial microvessels were common findings in the two groups receiving the atherogenic, calcification-inducing diet. However, these groups differed in the intensity of calcification: the deep part of the medial layer did not become calcified when the adventitia was resected. Moreover, adventitial regeneration was delayed in group II with respect to the animals that underwent adventitial resection without atherogenic, calcification-inducing diet. We conclude that this diet induced atherosclerotic lesions in the vessel wall and inhibited adventitial regeneration in the rats that underwent resection.