OBJECTIVES: In irritable bowel syndrome (IBS), the modulation of neural pathways may be altered and we have recently shown that postprandial recto-sigmoid tone modification is impaired. On pathophysiological grounds, we do not know whether this alteration may have a role in symptom onset and, in particular, whether an effective drug, such as tegaserod, can improve this response together with symptom severity. METHODS: Twenty-two female patients with constipation-predominant IBS (IBS-C), diagnosed according to Rome II criteria, were studied. All subjects underwent an evaluation of the presence and severity of IBS symptoms and the recto-sigmoid barostat test to measure fasting and postprandial recto-sigmoid tone and phasic contractility. They were then randomly assigned to receive either tegaserod 6 mg b.i.d (12 patients) or placebo tablets (10 patients) for 4 wk, according to a double-blind protocol. Symptom assessment and recto-sigmoid tone and contractility were re-evaluated at the end of the treatment. RESULTS: Both symptom severity and postprandial modification of recto-sigmoid tone improved only in the tegaserod group and a significant correlation was evident between the improvement of bloating and the improvement of postprandial recto-sigmoid tone modification. No effect of tegaserod on recto-sigmoid motility index or correlation between motility index and symptom improvement was evident. CONCLUSIONS: In IBS-C female patients, the administration of tegaserod improves symptom severity and is accompanied by an improvement of recto-sigmoid tone response to a meal.