Because approximately 80% of reported patients with somatostatinomas have gallstones, this study was performed to determine the effects of exogenous somatostatin on gallbladder emptying responses to liquid and solid meals, direct cholinergic stimulation by bethanechol, indirect cholinergic stimulation by sham feeding, and intravenously administered octapeptide of cholecystokinin. Gallbladder emptying was quantitated using 99mTc-HIDA and a gamma-camera on line to a digital computer. Somatostatin, administered at a dosage of 7 micrograms/kg X h, prevented the gallbladder emptying responses to both test meals, sham feeding, and bethanechol. The maximal gallbladder emptying response to octapeptide of cholecystokinin at 5.0 ng/kg X min was reduced from 93.2% +/- 4.8% to 57.1% +/- 9.9% (p less than 0.01) and to octapeptide of cholecystokinin at 0.5 ng/kg X min from 91.3% +/- 5.3% to 14.8% +/- 4.2% (p less than 0.01). These findings suggest that somatostatin is a potent inhibitor of gallbladder emptying in humans. This may be an important factor in the development of gallstones in patients with somatostatinomas.