We have recently described an association between irritable bowel syndrome (IBS) and abnormal lactulose breath test, suggesting small intestinal bacterial overgrowth (SIBO). However, the mechanism by which SIBO develops in IBS is unknown. In this case-control study we evaluate the role of small intestinal motility in subjects with IBS and SIBO. Small intestinal motility was studied in consecutive IBS subjects with SIBO on lactulose breath test. After fluoroscopic placement of an eight-channel water-perfused manometry catheter, 4-hr fasting recordings were obtained. Based on this, the number and duration of phase III was compared to 30 control subjects. To test whether there was a relationship between the motility abnormalities seen and the SIBO status of the patient at the time of the motility, subjects with a breath test within 5 days of the antroduodenal manometry were also compared. Sixty-eight subjects with IBS and SIBO were compared to controls. The number of phase III events was 0.7 +/- 0.8 in IBS subjects and 2.2 +/- 1.0 in controls (P < 0.000001). The duration of phase III was 305 +/- 123 sec in IBS subjects and 428 +/- 173 in controls (P < 0.001). Subjects whose SIBO was still present at the time of manometry had less frequent phase III events than subjects with eradicated overgrowth (P < 0.05). In conclusion, phase III is reduced in subjects with IBS and SIBO. Eradication of bacterial overgrowth seems to result in some normalization of motility.