Glucagon has been suggested for treatment of hypoxic liver conditions because it is reported to increase the splanchnic flow and portal oxygenation. With use of hepatic dearterialization in the pig as an experimental model for hepatic ischemia, the effect of glucagon on the release of serum glutamic oxaloacetic transaminase, serum lactic dehydrogenase, and the acid hydrolases, beta-glucosidase and beta-galactosidase, was studied. In control experiments, glucagon gave no enzymatic release. Dearterialization by itself caused a typical pattern of enzyme increases, especially of the acid hydrolases. Dearterialization in combination with glucagon showed a significantly higher release of the investigated enzymes and the animals were more affected by the operation. Autopsy revealed patchy necroses in the liver parenchyma, reasonably more widespread after glucagon administration. This unexpected result might be due to other than circulatory effects of glucagon, eg, depletion of liver glycogen and instability of lysosomal membranes.