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Background/aims: We have investigated the effect of acute hyperglycemia on pancreaticobiliary secretion and pancreatic polypeptide (PP) release., Methods: Duodenal outputs of bilirubin, trypsin, lipase, amylase and bicarbonate were measured using a recovery marker under basal conditions and in response to modified sham feeding (MSF) in 6 healthy subjects on two separate occasions: during normoglycemia and during acute hyperglycemia (15 mmol/l)., Results: During hyperglycemia the basal pancreaticobiliary output was significantly (p < 0.05) reduced. During normoglycemia MSF significantly (p < 0.05) increased the output of bilirubin and pancreatic enzymes; during hyperglycemia only the output of pancreatic enzymes increased significantly (p < 0.05) over basal. During MSF the outputs of bilirubin (16 +/- 4 vs. 4 +/- 2 micromol/30 min), trypsin (26 +/- 7 vs. 7 +/- 4 U/30 min), lipase (36 +/- 11 vs. 15 +/- 6 kU/30 min), amylase (3.4 +/- 0.7 vs. 1.4 +/- 0.7 kU/30 min) and bicarbonate (0.8 +/- 0.1 vs. 0.5 +/- 0.1 mmol/30 min) were significantly (p < 0.05) reduced during hyperglycemia compared to normoglycemia. During hyperglycemia basal and MSF-stimulated PP levels were significantly (p < 0.05) reduced compared to normoglycemia. MSF did not significantly influence plasma cholecystokinin levels in both experiments., Conclusions: This study indicates (1) that the blood glucose levels affect basal and cephalic stimulated pancreaticobiliary secretion and (2) that the PP secretion during hyperglycemia is reduced, suggesting impaired vagal cholinergic activity during hyperglycemia.