Administration of estrogen to cholesterol-fed rabbits dramatically retarded arterial lesion development despite its lack of effect on plasma cholesterol concentration and on lipoprotein patterns. Cholesteryl ester influx into the aortic wall was also much lower in the estrogen-treated animals and paralleled the aortic cholesterol content in treated and untreated animals; the fraction of aortic cholesteryl ester lost by efflux was the same in treated and untreated animals. The fraction of newly entered cholesteryl ester hydrolyzed by aorta was significantly reduced in the estrogen-treated animals. Low cholesteryl ester influx and relatively less hydrolysis of cholesteryl ester by the aorta may be indicative of reduced internalization of plasma cholesteryl ester by aortic cells, which may in turn account for the reduced atherogenesis in the estrogen-treated rabbits.