Serotonin (5-HT) may play an important role in the regulation of colonic motility in humans. However, it is not known whether alterations in the colonic 5-HT system are involved in the pathophysiology of irritable bowel syndrome (IBS). Colonic mucosal specimens ranging from the ascending colon to the rectum were obtained from patients with diarrhea-or constipation-predominant IBS (n= 7 and n= 8, respectively) and from subjects with normal bowel habits (n= 7) by endoscopic biopsy in order to determine whether patients with different clinical manifestations of IBS have different mucosal disposition of 5-HT. The tissue concentrations of 5-HT and its major metabolite, 5-hydroxyindoleacetic acid, were determined by reversed-phase high-performance liquid chromatography with fluorescence detection. In all study groups, the mean mucosal 5-HT concentrations obtained from the rectum were significantly (p< 0.05) higher than those obtained from more cephalic regions of the colon. In addition, the overall mean mucosal 5-HT concentrations obtained from patients with constipation-predominant IBS were significantly (p< 0.05) higher than those obtained from the control subjects and patients with diarrhea-predominant IBS. No significant differences were observed in 5-hydroxyindoleacetic acid concentrations among the three groups. The mucosal 5-HT concentrations in the colon showed an ascending cephalocaudal gradient in all study groups. Although the mucosal 5-HT concentrations were elevated in patients with constipation-predominant IBS as compared with those with diarrhea-predominant IBS and the control subjects, further studies are necessary to determine whether the elevated mucosal 5-HT is a cause or a result of abnormal colonic motility.