In order to investigate secretion of extrapancreatic glucagon in dogs, plasma glucagon and total immunoreactive glucagon (IRG) in response to arginine were determined with antisera specific and non-specific for pancreatic glucagon, respectively. Only a tiny rise of plasma glucagon was observed in the portal vein following arginine infusion performed immediately after total pancreatectomy in a group of 5 normal dogs. In contrast, total IRG in the portal vein increased significantly after arginine infusion even after pancreatectomy. In alloxan diabetic dogs, arginine infusion after total pancreatectomy caused a rise in plasma glucagon in the portal vein, although not significantly. The response of total IRG to arginine in the portal vein was exaggerated in alloxan diabetic dogs. In a group of one-week post-pancreatectomized animals, plasma glucagon and total IRG increased significantly in response to arginine infusion. Furthermore, in these dogs, response of plasma glucagon and plasma total IRG to arginine infusion was abolished after gastrectomy. From the present results it is concluded that secretion of extrapancreatic glucagon increased in response to arginine infusion in the diabetic state, both alloxan diabetic dogs and one-week post-pancreatectomized dogs. In addition, a rise in extrapancreatic glucagon following arginine infusion in the chronically pancreatectomized dogs almost certainly derived from the stomach, as the rise was abolished by gastrectomy.