The relationship between the molecular structure and insulin releasing action of glucagon remains unknown. In order to investigate the direct action of N-terminal peptides of glucagon, glucagon (1-14), and glucagon (1-21) were studied using an in situ local circulation of the canine pancreas. These glucagon fragments as well as glucagon (1-29) were infused into the superior pancreaticoduodenal artery in a dose of 400pmol for 10min during the glucose or arginine infusion, and plasma insulin and glucagon in the superior pancreaticoduodenal vein were determined by radioimmunoassay. During the glucose infusion, glucagon (1-14) elicited a slight increase in plasma insulin, whereas glucagon (1-21) and (1-29) revealed significant changes in plasma insulin. In these experiments plasma glucagon did not change significantly following the administration of glucagon (1-14) or (1-21). During the arginine infusion all of the glucagon fragments studied enhanced insulin secretion markedly, whereas glucagon secretion was not affected. Furthermore, graded doses of glucagon (1-14) (50, 150, and 400pmol) elicited an increase in plasma insulin in a dose-related manner. It is concluded from the present study that the N-terminal peptides of glucagon stimulate insulin release especially during the arginine infusion.- glucagon fragments; canine pancreas; arginine; glucose; insulin.