A single oral administration of natural principal estrogens, estrone (E1), 17 beta-estradiol (E2) and estriol (E3), caused active proliferation of hepatocytes of adult mouse liver. Steroid hormones tested (testosterone, progesterone and cortisone) other than estrogens were not stimulants of proliferation of hepatocytes. Among these three natural estrogens, E3 was found to be the most potent stimulant of hepatocyte proliferation and E1 was the weakest. The possible mechanism of the hepatocyte-proliferating potency of estrogens was discussed in close relationship to their stimulating effect on the reticuloendothelial system.