OBJECTIVE: In healthy individuals, intraluminal lipids delay intestinal gas clearance, and this reflex is exaggerated in patients with irritable bowel syndrome (IBS). Our aim was to determine the site of action of abnormal lipid-induced reflexes in IBS. METHODS: In six patients with (IBS) predominantly complaining of bloating and in six healthy subjects, a mixture of gas (N2, O2, and CO2 in venous proportions to minimize diffusion) was infused (12 mL/min) either into the jejunum or into the ileum for 2 h, with simultaneous perfusion of lipids (0.5 kcal/min) into the proximal duodenum. Rectal gas evacuation was measured by a barostat. Abdominal perception (by a 0-6 scale) and girth changes were measured at 15-min intervals. The effects of jejunal versus ileal gas infusion were compared by paired tests in random order on separate days. RESULTS: IBS patients exhibited significant gas retention during infusion of gas into the jejunum (398 ± 90 mL vs -210 ± 105 mL in health, p < 0.05) but not during ileal infusion (-79 ± 87 mL vs -79 ± 78 mL in health, NS; p < 0.05 vs jejunal infusion). Gas retention during jejunal gas infusion in IBS patients was associated with significant abdominal distension (11 ± 3 mm girth increment vs 0 ± 1 mm during ileal gas infusion and 1 ± 1 mm in health, p < 0.05 for both) and abdominal symptoms (3.6 ± 0.6 score vs 2.6 ± 0.7 score during ileal gas infusion and 1.6 ± 0.5 score in health, p < 0.05 for both). CONCLUSIONS: In IBS patients intraluminal lipids impair intestinal gas clearance because of upregulated reflex inhibition of small bowel transit, without appreciable colonic effects. © 2006 by Am. Coll. of Gastroenterology Published by Blackwell Publishing.