Enzymatically isolated aortic cells from control and cholesterol-fed rabbits were subjected to isopycnic density gradient centrifugation in Metrizamide. Control cells formed a single band equilibrating at a median density of 1.13 to 1.14, while cells isolated from atheromatous aortas formed two distinct bands, one equilibrating in the density range of 1.12 to 1.14 and the other occurring at a lower density of 1.03 to 1.07. Morphologically, the low density cells exhibited typical features of aortic foam cells. They were found to be greatly enriched in free and esterified cholesterol and in four lysosomal hydrolases. Further studies showed these cells to contain lipid-laden lysosomes. The high density cells from cholesterol-fed rabbits were also enriched in cholesterol and lysosomal enzymes compared to control aortic cells but not to the extent showen by the low density foam cells. While exhibiting the ultrastructural characteristics of smooth muscle cells, the cells in this fraction showed a considerable degree of morphologic and biochemical heterogeneity, suggesting the occurrence of many transition forms between normal smooth muscle cells and fully transformed foam cells.