Actual blood glucose concentrations influence gastrointestinal function. We investigated whether in healthy subjects the inhibitory effect of acute hyperglycemia on gallbladder motility is dose-dependent. Seven healthy volunteers were studied on four separate occasions in random order during euglycemia and during hyperglycemic clamping, at 4 mmol/l, 8 mmol/l, 12 mmol/l, and 16 mmol/l, respectively. Gallbladder volumes (ultrasonography) and plasma hormone release were studied before and after ingestion of a meal. Postprandial gallbladder contraction was significantly (P < 0.05) and dose-dependently inhibited during the hyperglycemic experiments at 8, 12, and 16 mmol/l (56%_8%, 49%_8%, and 30%_5%, respectively) compared with euglycemia (68%_6%). Postprandial cholecystokinin release was significantly (P < 0.05) reduced compared with euglycemia only at a plasma glucose level of 16 mmol/l (116_28 versus 159_13 pmol.l