The presence of methane on lactulose breath test among irritable bowel syndrome (IBS) subjects is highly associated with the constipation-predominant form. Therefore, we set out to determine whether methane gas can alter small intestinal motor function. In dogs, small intestinal fistulae were created to permit measurement of intestinal transit. Using a radiolabel, we evaluated transit during infusion of room air and subsequently methane. In this model, small intestinal infusion of methane produced a slowing of transit in all dogs by an average of 59%. In a second experiment, guinea pig ileum was pinned into an organ bath for the study of contractile activity in response to brush strokes applied to the mucosa. The force of contraction was measured both orad and aborad to the stimulus. The experiment was repeated while the bath was gassed with methane. Contractile activities orad and aborad to the stimulus were significantly augmented by methane compared with room air (P < 0.05). In a third experiment, humans with IBS who had undergone a small bowel motility study were compared such that subjects who produced methane on lactulose breath test were compared with those producing hydrogen. The motility index was significantly higher in methane-producing IBS patients (1,851 +/- 861) compared with hydrogen producers (1,199 +/- 301) (P < 0.05). Therefore, methane, a gaseous by-product of intestinal bacteria, slows small intestinal transit and appears to do so by augmenting small bowel contractile activity.