Vagotomy and gastric surgery have been implicated in gallstone formation, although the association remained unproven. Gallbladder function was investigated in 11 patients with a pyloroplasty and truncal vagotomy, 5 with a subtotal gastrectomy, and 16 healthy controls. Gallbladder filing and emptying in response to cholecystokinin (CCK 0.01 U/kg min), when quantitated by 99m-Tc-HIDA cholescintigraphy, did not show any differences between the control and the surgical groups. In each group, over 70% of hepatic activity partitioned into the gallbladder rather than the duodenum, filing the gallbladder at 2.1%/min. Gallbladder emptying began five minutes after initiating the CCK infusion and ejected half of its contents during the next 12 minutes. Biliary lipid compositions was determined in 20 patients who underwent elective pyloroplasty and vagotomy for duodenal ulcer disease. Gallbladder bile collected at surgery was compared to bile-rich duodenal fluid aspirated eight months after recovery from surgery. Cholesterol saturation decreased significantly (p less than 0.05) both in terms of the relative cholesterol content (6.9% leads to 5.2%) and the lithogenic index (1.24 leads to 0.84). To determine if a selective increase in one of the conjugated bile salts could explain this improvement, bile salt composition was analyzed by high pressure liquid chromatography in eight patients and showed no change after surgery. Thus, vagotomy does not adversely affect gallbladder function, but instead improves cholesterol solubility.