The mechanism of the contractile effect of domperidone on gallbladder smooth muscle has been investigated by using an in-vivo and an in-vitro model. In the in-vivo part of the study 14 healthy males were administered 20 mg domperidone or two placebo tablets orally and gallbladder emptying was measured by ultrasonography. The reduction in the gallbladder volume was significant compared to the placebo at 45 and 55 min. In the in-vitro part of the study, the gallbladder strips isolated from guinea pigs were field stimulated and 10(-6)-10(-4) M concentrations of dopamine were administered before electrical field stimulation (EFS) was repeated. Dopamine exerted no significant effect upon the contractions obtained by EFS. The effect of dopamine and domperidone under basal conditions were also explored. Under basal conditions, dopamine neither contracted nor relaxed the gallbladder muscle between 10(-6) and 10(-4) M concentrations when added directly to the organ bath. Besides, a significant contraction was observed with 10(-4) M concentration of domperidone whereas 10(-7), 10(-6) and 10(-5) M concentrations exerted no effect. This effect of domperidone was thought to be nonspecific but inhibited by 10(-6) M atropine, 10(-5) M pirenzepine and abolished by 10(-6) M tetrodotoxin. In summary, domperidone produces a modest contraction in human gallbladder. This effect does not seem to occur upon dopaminergic receptors in guinea pig models. (C) 1996 The Italian Pharmacological Society.