The effect of cisapride, a new non-antidopaminergic agent, on human gallbladder volume has been studied in nine normal subjects. In a double-blind crossover fashion, each subject was given a slow i.v. injection of cisapride and placebo after 12-h fasting. Gallbladder volume was monitored every 15 min for 90 min by real-time ultrasonography. After cisapride, gallbladder volume significantly diminished, with a mean reduction of 22.9 +/- 5%, observed 30 min after injection, whereas no significant changes were noted after placebo. A cholinergic mechanism is proposed to explain the effect of cisapride on gallbladder volume.