Impaired gallbladder contractility is a prerequisite for gallstone formation in animal models. Prostaglandins are important mediators of gallstone formation and may affect gallbladder contractility in animals. The aim of this study was to evaluate the effect of indomethacin, an inhibitor of prostaglandin synthesis, and misoprostol, a synthetic prostaglandin, on gallbladder contractility in man. Seven male volunteers (18–33 years old, mean age 23 years) were studied under blinded conditions after an overnight fast, during control periods and following ingestion of indomethacin 125 mg (75 mg at 10PM, 50 mg at 630AM) or misoprostol 800 g (400 g at 10 PM, 400 g at 630 AM) orally. Gallbladder residual volume was determined by real-time ultrasonography before and 10, 20, 30, 40, and 50 min after ingestion of a standard liquid fatty meal stimulus. Fasting gallbladder volume (milliliters) was similar in all three periods [control 20.8 (1.6);indomethacin 20.8 (2.9); misoprostol 18.3 (1.6)]. The fatty meal stimulus caused prompt contraction, resulting in minimum residual volume of 7.5 (1.4) ml in the control period. Pretreatment with misoprostol or indomethacin did not affect the minimum volume obtained compared with control period [misoprostol: 5.8 (1.4) ml; indomethacin 5.9 (1.3) ml)]. Thus administration of indomethacin and misoprostol had no effect on fasting gallbladder volume or gallbladder contractility in humans as assessed by ultrasonography.