Research in dogs and baboons involving the identification and manipulation of portal venous hepatotrophic substances. Studies with surgical procedures which divide the splanchnic venous drainage to the liver into pancreatic and intestinal components have shown that the major hepatotrophic influence is from the pancreas. Other studies using animals made diabetic with alloxan or pancreatectomy have shown insulin to be the most important hepatotrophic factor. Diversion away from the liver of these portal hepatotrophic factors adversely affects hepatocyte size and replication, depletes glycogen storage and depresses cholesterol and triglyceride synthesis. Work in progress or planned for the coming year will compare acute regeneration after hepatic resection in liver lobes supplied with or deprived of hepatotrophic substances. Similarly, the influence of hepatotrophic factors upon recovery after acute liver injury will also be studied. It was shown during the current year that portal diversion has an antilipidemic effect in normal dogs; these observations will be extended in animals with exogenous hyperlipidemia. Finally, the incidence, severity and treatment of dogs and baboons showing encephalopathy ("meat intoxication") after portacaval shunt will be investigated.