The innominate artery is a predilection site for atherosclerotic lesion formation in hyperlipidemic mice. The lesions at this site in chow-fed apo E-/- mice progress from fatty streaks through stages that include atheroma with large necrotic areas, fibro-fatty nodules containing chondrocyte-like cells and highly calcified, acellular plaques. The advanced lesions in the innominate arteries of the apo E-/- mice exhibit a reproducible frequency of intra-plaque hemorrhage that occurs primarily as a result of fissures through lateral fatty streaks that form adjacent to or on top of the established plaques. However, this plaque disruption is not equivalent to plaque rupture in human lesions where there is rupture of well formed fibrous caps. The plaque disruption in the lesions of the chow-fed apo E-/- mice also do not lead to formation of occlusive thrombi, the predominant marker of plaque rupture in humans. Thus, although the lesions in the innominate arteries of hyperlipidemic mice progress to very advanced stages of the disease, they are not, in our opinion a model in which to study the mechanisms of plaque rupture in humans. The advanced lesions in the innominate arteries of the apo E-/- mice may however be adequate models for studying vascular fibrosis and calcification.