Watanabe Heritable Hyperlipidemic (WHHL) and cholesterol-fed New Zealand White (CH-FED NZW) rabbits were sacrificed at 15 months of age or after 16 weeks of cholesterol feeding, respectively. During the experimental period, the arterial walls of both the CH-FED NZW and WHHL rabbits were exposed to similar amounts of cholesterol and the lesions which developed at the aortic arch had similar intimal thicknesses, total lipid and cholesterol content. However, the lesions of the WHHL rabbits morphologically resembled human plaques, and contained lipid in the form of smectic liquid crystalline droplets and cholesterol monohydrate crystals. The CH-FED NZW rabbits had lesions which were fatty streak-like, containing liquid crystalline cholesteryl ester droplets but few crystals. The aortic arch intimas of the CH-FED NZW rabbits contained significantly more cholesteryl ester, and less unesterified cholesterol and triglyceride, than those of the WHHL rabbits. The intimal compositions of the two rabbit models did not overlap. Analysis of the compositions predicted precipitation of cholesterol monohydrate crystals in the WHHL but not the CH-FED NZW. The physical state of the deposited cholesterol esters was similar in both with about half being in smectic liquid crystalline form at body temperature. Since the size and total lipid content of the lesions of the CH-FED NZW and WHHL rabbits were similar, we suggest that the greater time of exposure to hypercholesterolemia was important in the formation of cholesterol monohydrate crystal-containing plaques in the aortic arch of the WHHL rabbits.