BACKGROUND: It is unclear whether decreased serotonin transporter function contributes to sensorimotor abnormalities in irritable bowel syndrome. AIM: To study the influence of acute serotonin transporter inhibition on colonic sensorimotor function in man. METHODS: Ten healthy subjects (five men, aged 20-29 years) underwent a combined manometry/barostat study of the descending colon on two occasions. Stepwise distentions by 2 mmHg increments were performed until discomfort. Subsequently, placebo or citalopram 20 mg were administered i.v. over 20 min and distentions were repeated. Afterwards, isobaric tone measurements were performed 30 min before and 90 min after ingestion of a meal. High-amplitude propagated contractions, colonic motility index, colonic compliance, sensitivity and colonic response to a meal after placebo or citalopram were compared by t-test and two-way ANOVA. RESULTS: Citalopram induced a significant increase in colonic motility index (5.6 +/- 0.9 to 0.8 +/- 1.9 mL*min, P < 0.005) and high-amplitude propagated contractions (32 after citalopram vs. 2 after placebo, P < 0.05), which were associated with abdominal cramping. Administration of citalopram increased colonic compliance (10.3 +/- 1.5 vs. 14.5 +/- 2.2 mL/mmHg, P < 0.01) and inhibited colonic response to a meal (volume decrease 48 +/- 12 vs. 16 +/- 12 mL, P < 0.01). CONCLUSIONS: Acute serotonin transporter inhibition in man increases colonic phasic contractility and the occurrence of high-amplitude propagated contractions, increases colonic compliance and suppresses the colonic tonic response to a meal. These data suggest that both release and elimination of 5-hydroxytryptamine by serotonin transporter are involved in the control of colonic motility in man.