Immunoreactive glucagon (using 30K antibodies) and insulin concentrations in the superior pancreaticoduodenal (pancreatic) vein of anesthetized mongrel dogs were measured after administration of 2-bromo-α-ergocryptine (CB154), γ-aminobutyric acid (GABA), and γ-hydroxybutyric acid (GHB) into the superior pancreaticoduodenal artery. A bolus administration of CB154 (200 μg/kg) induced a hyperglycemic response with biphagic increases in plasma glucagon and insulin levels. Blood pressure was lowered after a transient slight elevation. Impedance in pancreatic tissue was markedly increased after an initial rapid decrease. The lowered impedance reflects increased blood flow in the tissue. CB154 (50 μg/kg) administration brought about hyperglycemia and mild hyperglucagonemia. However, the plasma insulin level did not vary. After premedication with pimozide (1 mg/kg, intramuscularly), CB154 (200 μg/kg) administration caused a mild gradual increase of blood glucose, mild increase of plasma glucagon and significant decrease of plasma insulin concentrations. The premedication had no effect on blood pressure changes. Impedance in pancreatic tissue was slightly increased after a mild transient decrease. GABA (5 mg/kg) infusion for 30 min induced mild hyperglycemia, biphasic increase of pancreatic plasma glucagon and biphasic decrease of pancreatic plasma insulin concentrations. Blood pressure rose slightly, then gradually fell after a few minutes. Impedance in pancreatic tissue increased slowly. With a GABA (1 mg/kg) infusion for 5 min, the pancreatic plasma glucagon level gradually rose, and the plasma insulin level fell. During a GABA infusion at a dose of 0.1 mg/kg for 5 min, the plasma glucagon level increased slightly, but the plasma insulin level did not vary. A GHB (500 mg/kg for 2 min) infusion brought about a mild transient hyperglycemia. Although there was an initial decrease in the glucagon concentration, the amount of secreted glucagon seemed unchanged since the volume of blood flow in pancreatic tissue increased markedly during this period. The biphasic increase in glucagon concentration followed. Plasma insulin concentrations decreased significantly. GHB administration at a dose of 100 mg/kg for 2 min had similar effects on insulin and glucagon secretion, and did not cause any change in blood glucose level. The changes in plasma glucagon and insulin levels during 5 min infusion of GHB (100 mg/kg) were tested in more detail. The level of glucagon decreased slightly followed by a gradual increase after a few minutes. The plasma insulin level decreased significantly. GHB (10 mg/kg) infusion for 5 min resulted in no change of plasma glucagon concentration and a mild decrease in plasma insulin concentration.