BACKGROUND: The irritable bowel syndrome (IBS) is associated with motor abnormalities in the small intestine and colon. Neuropeptides may have an important role in initiating and regulating the intestinal motility. Motilin has been proposed to initiate the peristaltic reflex in the small intestine and cholecystokinin the gastrocolic reflex. METHODS: In 18 patients with IBS and 11 healthy control subjects plasma motilin and cholecystokinin (CCK) concentrations were measured after intraluminal stimulation of water and a fat-rich meal. RESULTS: The IBS patients had reduced motilin secretion after both water intake and the fat meal. In contrast, the fat meal elicited an exaggerated and prolonged CCK release in the IBS patients. CONCLUSIONS: Disturbed motilin and CCK release may partly be responsible for the intestinal dysmotility in the IBS patients.