The risk of developing gallstones is increased in obese subjects. We have investigated whether gallbladder motility in obese subjects is different from that in lean control subjects. In 25 healthy non-diabetic obese subjects and 20 age- and sex-matched lean controls, fasting gallbladder volumes, gallbladder contraction in response to cephalic vagal cholinergic stimulation by modified sham feeding (MSF) and to hormonal stimulation with cholecystokinin (CCK) were studied. Gallbladder volumes were measured during a 30-min MSF period followed 1 h later by a 1-hour continuous i.v. infusion of 0.5 IDU/kg ideal weight of CCK-33. Fasting gallbladder volumes were significantly (p < 0.001) larger in obese (47 +/- 4 cm3) compared to lean subjects (24 +/- 2 cm3). Fasting gallbladder volume was correlated with body mass index (p < 0.01). Gallbladder contraction during MSF was significantly (p < 0.01) reduced in obese (12 +/- 2%) compared to lean subjects (22 +/- 3%). CCK infusion, leading to physiological post-prandial plasma CCK levels, induced a significantly (p < 0.001) greater absolute gallbladder contraction in obese (27 +/- 3 cm3) compared to lean subjects (15 +/- 1 cm3) but the percentage gallbladder contraction was in the same range (64 +/- 3% vs. 67 +/- 4%, respectively). In addition, residual gallbladder volumes after CCK infusion were significantly (p < 0.001) larger in obese (15 +/- 2 cm3) than in lean subjects (7 +/- 1 cm3). Two groups of obese subjects were identified: one with increased (>40 cm3) and one with normal (< or = 40 cm3) fasting gallbladder volumes. Only obese subjects with increased fasting volumes showed abnormal gallbladder motility.