Previous studies have provided conflicting results of cisapride on gallbladder emptying in response to a meal. We studied six volunteers and six patients after a truncal vagotomy in a double-blind, placebo-controlled, prospectively randomized study using 10 mg cisapride four times a day for three days. Gallbladder volume was quantitated using ultrasonography, and plasma CCK levels were measured with a sensitive and specific radioimmunoassay using the DINO antibody before and for 90 min after a fatty, mixed meal. Plasma effect was observed on the gallbladder either in normal subjects or vagotomized patients. Paradoxically, residual volume (RV) was increased in the vagotomized patients after treatment with cisapride: RV cisapride 7.1 (4.1-15.9) ml, RV placebo 5.1 (3.8-14) ml, P < 0.05. Further work is required to clarify the mechanisms of action of cisapride on the gallbladder and the sphincter of Oddi. The use of cisapride during litholytic therapy may impair gallbladder emptying and delay stone clearance.