The purpose of this study was to investigate the role of arginine-vasopressin (AVP) on glucagons secretion in both normal and diabetic rats. Diabetes was induced by intraperitoneal administration of alloxan HCI(200 mg/kg). Both glucagon and AVP were determined in the effluent of the perfused pancreas using radioimmunoassay. Diabetic rats had higher baseline glucagons concentrations than normal rats. AVP (1 pmol/L) failed to change glucagons secretion in normal rats, but significantly increased glucagons secretion in diabetic rats. AVP (10-100 pmol/L) increased glucagons secretion from both normal and diabetic rats in a concentration dependent manner. However, diabetic rats were more sensitive to AVP administration than normal rats with regard to glucagon secretion. By comparison of the areas under the curves, the glucagons secretion induced by AVP in diabetic rats was ~2-fold that of the normal rats. In addition, we determined whether AVP was secreted from the pancreas. Immunoreactive AVP was detected in the effluent of the perfused pancreas, and diabetic rats had 2-fold higher AVP concentrations in the pancreatic effluent than normal rats. We conclude that AVP is secreted from the pancreas and diabetic rats secrete more AVP from the pancreas than normals. Consequently, AVP may have a greater impact on glucagons secretion in diabetic rats than normals. AVP might play an important role in the hypersecretion of glucagons, a hyperglycemic hormone, in diabetic animals.