The effects of synthetic neurotensin and xenopsin on plasma glucagon and insulin secretion were investigated using dogs. Neurotensin and xenopsin were injected rapidly or infused for 30 min into the superior pancreaticoduodenal artery. Plasma glucagon and insulin in the superior pancreaticoduodenal (pancreatic) vein and femoral vein were measured by radioimmunoassay. In normal dogs, rapid administration of neurotensin (10μg/kg body weight) brought about mild hyperglycemia and a rapid and sharp increase of plasma glucagon and insulin levels in the pancreatic and femoral veins. Though the plasma glucagon level in the pancreatic vein showed a nider at 45 min, the glucagon response maintained a significant increase for 120 min. A biphasic insulin response with the second peak at 30 min was noted in the pancreatic and femoral veins. The blood pressure was 30% of the initial value at 2 min after neurotensin administration and returned to the initial level at the end of the experiment. An insignificant elevation of the plasma cortisol level was observed after neurotensin administration. These vaso-circulatory changes and the increase of plasma cortisol concentration by neurotensin administration were assumed to influence the increase of glucagon in the latter period of the experiment and the formation of second peak of insulin level. In normal dogs, neurotensin (0.5μg/kg/min) infusion brought about mild hyperglycemia and a rapid and sharp increase of plasma glucagon and insulin in the pancreatic and femoral veins, during the infused period of 30min; however these responses were smaller than those for the rapidly injected neurotensin. In hypophysectomized dogs, the basal level of plasma glucose, pancreatic glucagon and insulin decreased to 52% , 48% , 11% of normal dogs respectively. Neurotensin (10μg/kg body weight) administration resulted in no elevation of blood glucose. Neurotensin has little effect on glucagon and insulin secretion. A biphasic insulin secretory pattern observed in normal dogs was not demonstrated in hypophysectomized dogs. It seems that the pituitary gland plays some role in the neurotensin-induced insulin secretion. In normal dogs, rapid administration of xenopsin (10μg/kg body weight) brought about mild hyperglycemia and a rapid and sharp increase of plasma glucagon and insulin in the pancreatic and femoral veins. Glucagon secretory activities were the same as with neurotensin but insulin secretory activities were smaller. Neurotensin and xenopsin appeared more potent inducers of glucagon in the present experiment. Neurotensin and xenopsin appeared to stimulate glucagon and insulin secretion not only by neurogenic vasodilatation, but also by a direct action on pancreatic alpha and beta cells.