The concentrations of plasma high density lipoprotein (HDL) and its subtraction HDL2 are influenced by endogenous and exogenous sex hormones. The catabolism of HDL2 is mediated by a lipolytic enzyme, hepatic lipase, which is present in endothelial cells covering the liver sinusoids. Since the activity of this enzyme is also regulated by gonadal and anabolic steroids, we examined whether the effect of sex steroids on plasma HDL is related to changes in hepatic lipase. In postmenopausal women, estradiol valerate (2 mg/day, orally) increased the HDL2 cholesterol and phospholipid concentrations by 20% (P 2 cholesterol and phospholipid levels fell below and hepatic lipase activity rose above the respective pretreatment values. The hormones did not influence the HDL3 lipid concentrations or the lipoprotein lipase and lecithinxholesterol acyltransferase activities. The results are compatible with the hypothesis that the effects of sex steroids on plasma HDL (HDL2) are mediated by changes in hepatic lipase activity. (J Clin Endocrinol Metab54: 1113,1982)