A kinetic study of different processes of hepatic glucagon metabolism has been performed using the model of recycling perfused rat liver. Glucagon was eliminated in a concentration dependent fashion from the circulation. The initial rates of hepatic glucagon extraction were rather small, and did not exceed 2.8 +/- 0.2% of the initial glucagon mass flow of 9.6 +/- 0.0 ng/min. The major portion of glucagon was eliminated within the first 10 min of perfusion. Both binding and internalization of glucagon were the dominating processes in this phase. After 10 min of perfusion, an acceleration of glucagon degradation was observed leading to the release of cleavage products into the perfusate. The physiological role of glucagon degradation and its possible relation to the termination of the hepatic glucagon action is still unknown. The present results suggest that the liver seems not to be of primary importance for systemic glucagon degradation.