The surface membrane of the hepatic parenchymal cell is a dynamic structure composed of protein, lipid, and carbohydrate. The protein components of cell membranes consist of many species with a wide range of molecular weights and rates of degradation. Our previous studies demonstrated alteration of specific canalicular enzymes in both severe cholestasis produced by bile duct ligation and mild cholestasis following ethinyl estradiol administration. Recent studies demonstrate decreased activity of hepatic microsomal mixed function oxidase system enzymes also. Current studies are investigating the effect of both severe and mild cholestasis of the synthesis and degradation of specific membrane proteins. The following investigations will be performed: 1. relative synthesis and degradation rates of microsomal and plasma membrane proteins separated by SDS-polyacrylamide gel electrophoresis following cholestasis and administration of pharmacologic agents, 2. relative synthesis of membrane glycoproteins in cholestasis, 3. synthesis, transport and degradation of microsomal P450 and alkaline phosphatase.