OBJECTIVE: Irritable bowel syndrome (IBS) has been associated with psychiatric comorbidity and alterations in serotonergic metabolism. Tryptophan is the precursor of serotonin (5-HT), but it is mainly catabolized through the kynurenine pathway. This pathway may also be involved in the pathogenesis of IBS by virtue of deviating tryptophan from the 5-HT pathway resulting in 5-HT deficiency. We therefore aimed to ascertain the mucosal and systemic concentrations of 5-HT and kynurenic acid (KYNA), a principal kynurenine metabolite. METHODS: Duodenal mucosal biopsy specimens and platelet poor plasma samples were obtained from 15 healthy volunteers and 15 IBS patients. Psychological state was assessed using the Hospital Anxiety and Depression Scale and the Symptom Checklist-90. RESULTS: IBS patients showed significantly lower mucosal and higher systemic concentrations of both 5-HT and KYNA compared to healthy controls. Also, significant correlation between mucosal but not plasma concentrations of KYNA and 5-HT and psychological state in IBS was observed. CONCLUSION: The observation that mucosal KYNA and 5-HT are both decreased in IBS does not support the hypothesis that increased activation along the kynurenic pathway results in relative 5-HT deficiency. However, an increased release of these substances from the intestine to the systemic compartment may lead to a decrease in intestinal KYNA and 5-HT levels, resulting in disturbance of intestinal homeostasis. Thus, changes in psychological states observed in IBS patients may be secondary to alterations in gastrointestinal function, and in particular kynurenine and/or 5-HT metabolism.