Nine female Yucatan miniature swine, a breed not previously evaluated for their potential usefulness as a model for experimental atherosclerosis studies, were fed a high-fat, high-cholesterol diet for 10-12 months. These swine and 4 control (low-fat, low-cholesterol-fed) swine underwent a complete necropsy at the end of this period to characterize the atherosclerosis both by gross and microscopic examination. Cholesterol feeding led to elevated serum cholesterol levels and the development of accelerated atherosclerosis. Control animals on a low-cholesterol diet had little gross or microscopic atherosclerosis. All of the cholesterol-fed swine had more extensive atherosclerosis than any of the controls by gross inspection of the Sudan-stained arterial tissue. There was individual variation suggesting the interaction of factors in addition to the plasma cholesterol which determine the extent and severity of atherosclerosis. However, it was possible to show a positive correlation between hypercholesterolemia and (1) intimal thickening in the terminal abdominal aorta and mesenteric artery, and (2) increased fat deposition in the mesenteric artery. The cholesterol-induced atherosclerosis was characterized by the deposition of lipid in and around cells. Complicated atherosclerotic lesions similar to human atherosclerosis were characterized by marked animal proliferation, necrosis, cholesterol crystal deposition, and calcification. It is concluded that the Yucatan miniature swine represent an important additional animal model in which to study certain aspects of atherosclerosis.