There is little information about the effects of cisapride on human antropyloroduodenal motility, despite its documented efficacy for increasing the rate of gastric emptying in patients with gastroparesis. Cisapride has been reported to have little effect on gastric emptying in normal subjects. Antral, pyloric, and duodenal pressures were recorded simultaneously with gastric emptying in 20 healthy volunteers. Thirty minutes after the solid component of the meal had started to empty from the stomach, each subject received either 10 mg cisapride i.v. (11 subjects) or intravenous saline (9 subjects). Intravenous saline had no effect on either motility or gastric emptying. In contrast, cisapride administration was associated with a dual effect on motility, with initial suppression of antral pressure waves (P < 0.05) followed by stimulation of associated antropyloroduodenal pressure waves (P < 0.01). Gastric emptying slowed in the first 30 min after cisapride (P < 0.05), and this was followed by more rapid gastric emptying (P < 0.01). The amount of the meal emptied in the 60 min after cisapride correlated with the number of associated antroduodenal pressure waves (r = 0.75, P < 0.001) but not with the number of antral waves (r = 0.42, NS). These results indicate that cisapride in a dose of 10 mg i.v. has dual effects on gastric emptying and gastric motility. The stimulation of associated antral pressure waves is a plausible mechanism for the efficacy of cisapride in the treatment of gastroparesis.