These studies are designed to evaluate the content and activity of bile canalicular enriched liver plasma membrane (LPM) enzymes as they are modified by factors which alter the rate of bile secretion. Special attention is given to the relationship of LPM Na ion, K ion-ATPase activity, sodium transport, and bile salt independent canalicular flow as they are influenced by various hormones, drugs and endogenous and synthetic bile acids. SDS gel electrophoresis will be used to separate LPM proteins to determine the effects of choleretic and cholestatic aspects on LPM proteins and their turnover and to identify those proteins that are affected by alterations in bile secretory function. The effects of hormones, drugs and bile on canalicular membrane enzymes will be correlated with their secretory effects as well as their effects on structural changes as determined by electron and scanning electorn microscopy. Structure-functional relationships between bile secretory function and the composition of bile canalicular membranes will be established.