This preliminary report describes the simplest and possibly earliest lipid-containing lesions induced in aortas of rabbits fed a cholesterol-containing diet. Subendothelial accumulation of unesterified cholesterol, detected with filipin dye, appears to precede morphologic changes in endothelium and accumulation of subendothelial lipid-containing "foam" cells. The origin of subendothelial unesterified cholesterol remains to be determined.