BACKGROUND Administration of 5-hydroxytryptamine (5HT) and selective 5HT receptor ligands modifies interdigestive motility in animals and in man. OBJECTIVE To study the effect of citalopram, a selective 5-HT reuptake inhibitor, on interdigestive motility in man. METHODS In 20 healthy subjects, antroduodenojejunal motor activity was studied manometrically. Basal interdigestive motor activity was recorded until the passage of two activity fronts. Ten minutes after the second activity front, placebo or 20 mg of citalopram was administered intravenously in a double-blind randomized fashion. Recording continued until the passage of two more activity fronts had occurred. RESULTS Administration of citalopram induced a premature small intestinal phase 3 after 35 +/- 6.4 min, compared to 120 +/- 17 min after placebo P < 0.01. Citalopram shortened MMC cycle length at the expense of phase 1 and phase 2 and significantly increased the motility index during phase 2 in the antrum and the small intestine. CONCLUSIONS In the interdigestive state in man, intravenous administration of the selective 5-HT reuptake inhibitor citalopram induces a premature intestinal phase 3 and suppresses gastric activity fronts. Phase 2 motility is stimulated both in the stomach and in the small bowel after citalopram. These data suggest that 5HT is involved in the control of interdigestive motility.