Gallbladder stasis is frequent in obese subjects and may contribute to their increased risk for gallstone formation. The bile salt sequestrant cholestyramine acutely enhances postprandial gallbladder emptying in lean subjects, through disinhibition of a negative feedback between intraluminal bile salts and CCK release. In this study the effect of cholestyramine on both gallbladder and gastric antrum dynamics were studied by real-time ultrasonography in 12 obese and 15 lean subjects. For the acute study, on different days, subjects ingested a liquid meal (two egg yolks plus water 200 mL, 50 kJ) or a meal with 4 g cholestyramine. Gallbladder emptying was impaired in obese patients who had significantly larger fasting gallbladder volume (39.4 +/- 6.9 vs. 21.6 +/- 1.7 mL, P < 0.02), larger residual volume (12.3 +/- 1.8 vs. 4.0 +/- 0.5 ml, P < 0.0006) and slower emptying time (T/2: 33 +/- 2 vs. 21 +/- 2 min, P < 0.05) than lean subjects. Integrated antral emptying was also less in obese than lean subjects (5521 +/- 578 vs. 7908 +/- 491 %120 min-1, P < 0.02). Cholestyramine enhanced postprandial gallbladder emptying in both obese and lean subjects. Gastric emptying was delayed with cholestyramine in lean but not obese subjects. For the chronic study, after 1 month therapy with cholestyramine (4 g every 2 days), the motility tests were repeated in nine obese subjects. Gallbladder and gastric responses to a test meal, with or without cholestyramine, were preserved. We conclude that both gallbladder and antral emptying of a liquid test meal are impaired in obese subjects. Gallbladder emptying improves after acute administration of a low dose cholestyramine with test meal. This effect is sustained after 1 month treatment with a low dose of cholestyramine and does not interfere with gastric emptying of obese patients. Cholestyramine may improve gallbladder hypomotility in obese people.