Intravenous cisapride was shown to induce a phase-2-like pattern of human interdigestive jejunal motor activity containing an increased number of propagated contractions. This study investigated the effects of oral cisapride in 12 fasting healthy males. Jejunal pressures were recorded by a pneumohydraulic system and five catheter orifices positioned 10-30 cm aborad the ligament of Treitz. Single oral doses of 5 and 10 mg cisapride, administered 5 min after an activity front under random double-blind conditions, induced a phase-2-like jejunal motor pattern with a significantly higher number and amplitude of contractions and significantly more aborally propagated waves than placebo (P less than 0.001), while the number of subjects with activity fronts decreased with increasing dose. Five and 10 mg cisapride administered tid for three days affected psychomotor function, subjective feelings, and side-effect frequency, apart from increases in systolic blood pressure and heart rate, no more than placebo. It is concluded that in fasting man, oral cisapride induces a highly propagative phase-2-like jejunal motor pattern causing only minor side effects.