The development of advanced coronary atherosclerosis was studied in the FHC swine. This model exhibits spontaneous elevations in plasma cholesterol, LDL, and apo B while fed a low-cholesterol, low-fat diet. Hypercholesterolemic animals bearing the apo B genotypes Lpb2/3, 3/3, 3/5, 5/5 and 3/8 developed stenotic coronary lesions containing necrotic cores, fibrous caps, calcification, neovascularization, hemorrhage, and fissuring. Myocardial infarction and myocardial ischemia were also observed. The complicated atherosclerotic plaques observed in this swine model closely resemble advanced coronary artery disease (CAD) found in humans. While coronary atherosclerosis was not observed in the absence of hypercholesterolemia, neither the apo B genotype nor the level of hypercholesterolemia was found to predict the extent of lesion formation. Similar to the case in humans, the familial dyslipidemia associated with the development of CAD in the FHC swine appears to be polygenic.