Background: Gas pooling within the gut may produce abdominal symptoms but the segment of the intestine responsible for gas retention is unknown. Our aim was to determine the role of the proximal and distal bowel in symptomatic gas accumulation using an experimental model of gas retention triggered by intraluminal lipids. Subjects: Sixteen healthy subjects. Methods: A gas mixture (N2, O2, and CO2 in venous proportions) was infused into the intestine at 12 ml/min for three hours and gas evacuation was continuously measured via an anal cannula connected to a barostat. Abdominal perception and girth changes were measured at 10 minute intervals. Lipids (1 kcal/ min) were simultaneously perfused either into the duodenum (n=8) or into the ileum (n=8). Each subject was studied twice on separate days, with gas infused into the jejunum or ileum. Results: Duodenal lipids produced retention of gas infused into the jejunum (646 (62) ml) but the volume retained was much smaller when gas was infused directly into the ileum (262 (90) ml; p<0.05). The effects on gas retention were even more pronounced during ileal perfusion of lipids (1546 (184) ml during jejunal gas infusion and 847 (142) ml during ileal gas infusion; p<0.05). Abdominal distension correlated with the volume of gas retained (r=0.87; p<0.001). Healthy subjects tolerated gas retention, and significant symptoms (score 3.7 (0.8)) developed only during jejunal gas infusion plus ileal lipid perfusion when gas retention was very large. Conclusion: Intraluminal lipids induce intestinal gas retention, predominantly acting on the proximal small bowel.