Impaired gallbladder emptying has been associated with gallstone disease but any effect on or from bile acid therapy for gallstone dissolution is unknown. We evaluated gallbladder filling and emptying with low-dose cholecystokinin infusion (0.02 U/kg.h) by computer-assisted cholescintigraphy in 52 controls versus 31 gallstone patients: 17 treated with 12-15 mg/kg.day of chenodeoxycholic acid and 14 with 8-10 mg/kg.day of ursodeoxycholic acid. Thirteen of 31 patients with complete dissolution had four scans: before, after 3 mo of therapy, after stone dissolution, and after discontinuation of bile acids. The 18 failures had three scans: before and after 3 and 15-18 mo of therapy. Before therapy, the 31 gallstone patients had significantly impaired gallbladder emptying compared with controls, but filling was not decreased. Bile acids significantly decreased emptying in both treatment groups after 3 mo of therapy. In the dissolution group, emptying improved once the stones had dissolved and increased further upon discontinuing the bile acids. In the failures, impaired emptying persisted for up to 15-18 mo. Gallbladder filling in the 31 gallstone patients was also significantly decreased after 3 mo of bile acid therapy, particularly in the failure patients, 5 of whom exhibited zero filling. No differences were detected between ursodeoxycholic acid and chenodeoxycholic acid for either gallbladder function or efficiency of dissolution. Thus, bile acid therapy impairs gallbladder filling and emptying in gallstone patients. Gallstone dissolution improves emptying, which is further enhanced when bile acids are discontinued.