In human as well as animal atherosclerosis, the bulk of lipids accumulates in lesions in the form of small spheres. We have studied these particulate lipids in human fatty streak and fibrous plaque lesions, and determined their average diameter as 1.9μ and defined their liquid crystalline nature as lyotropic smectic mesophase. We have designated these lipid bodies in atherosclerosis as lipid inclusions.In this study we isolated these lipid inclusions from fatty streak and fibrous plaque lesions of aortic atherosclerosis of each 21 subjects, with an average age of 40.9 and 51.2, respectively, who died sudden and unexpected death. Lipids were analysed by quantitative thin-layer chromatography and cholesteryl ester fatty acids by gas-liquid chromatography for comparison between inclusions and inclusion-free tissue residues, and also between the inclusions of fatty streak and fibrous plaque lesions.The compositions of lipids of the inclusions were remarkably uniform and strikingly different from those of inclusion-free residues, respectively: cholesteryl esters 82.3 vs 34.6% free cholesterol 4.9 vs 20.4%, triglycerides 4.3 vs 4.8%, and total phospholipids 8.7 vs 40.1% in fatty streaks, and cholesteryl esters 60.8 vs 42.0%, free cholesterol 13.0 vs 28.9%, triglycerides 10.4 vs 6.3% and total phospholipids 15.8 vs 22.9% in fibrous plaques. The proportions of individual phospholipids were also different in lecithin and sphingomyelin between the inclusions and the residues in fatty streaks. The compositions of inclusions of fatty streaks were significantly different from those of fibrous plaque inclusions with the exception of triglycerides and lysolecithin. Major fatty acid of cholesteryl esters in both fatty streak and fibrous plaque inclusions was oleate.These results indicate that (i) the lipid inclusions from both fatty streaks and fibrous plaques are quite unique in the chemical compositions when compared with those of any other blood lipids or serum lipoproteins such as chylomicron, VLDL, LDL, and HDL. (ii) that the metabolic origin of the lipid inclusions, therefore, cannot be explained by a simple deposition of blood lipid constituents or serum lipoproteins in the lesion tissues, and (iii) that the liquid crystalline nature of the inclusions largly due to physical properties of cholesteryl ester molecules seems to be playing a crucial role in the pathogenesis and development of fatty streak and fibrous plaque lesions.