The present studies examine the modulation of lipoprotein metabolism at subcellular sites in the liver by female sex hormones. Subcutaneous injection of ethinyl estradiol (5 mg/kg) decreased both triacylglycerol (TG) lipase activity and neutral cholesteryl ester (CE) hydrolase activity in hepatic endosomes while increasing lysosomal lipid hydrolysis. These data suggest that estrogen may induce a shift in the site of intracellular lipid catabolism similar to that found in fasting animals [1]. This work also shows that TG-lipase activity is increased in the CURL and MVB endosomal fractions of ovariectomized rats compared to that found in the equivalent endosomal compartments of age-matched intact female controls. These observations are consistent with an inhibition of endosomal lipase by female sex hormones under physiologic conditions.