Hypercholesterolemia induces atheroma formation, and the concentration of sphingomyelin is increased compared with that in the normal aortic intima-media. The aortic intima-media sphingomyelin concentration appears to increase exponentially with time on the cholesterol diet. Moreover, the entry rate of serum sphingomyelin into the aortic wall also appears to increase exponentially with time on the cholesterol diet and with the extent of aortic exposure to hypercholesterolemia. 32P-Phosphate incorporation into sphingomyelin and other phospholipids in the perfused rabbit aorta does not increase with atheromatosis, but the rate of sphingomyelin entry increases 27-fold during approximately the same period of atheroma formation and can account for all of the increase in sphingomyelin concentration in the intima-media.