BACKGROUND The dramatic inhibitory effect of proton pump inhibitors on acid secretion has raised concern about possible side-effects, such as small bowel bacterial overgrowth, which may result in further gut dysfunction. The aim of this study was to assess the effect of proton pump inhibitors on duodenal bacteriology, carbohydrate absorption and bowel habit. METHODS Small bowel bacterial overgrowth and xylose absorption were measured by culture of aspirated duodenal fluid and a combined 1 g 14C-D-xylose absorption-metabolism test in 20 patients with peptic ulcer disease. Tests were repeated after 4 weeks of treatment with omeprazole 20 mg daily. Intestinal transit was assessed by recording interdefecatory intervals and stool form. RESULTS All patients showed an increase in duodenal bacterial counts following treatment, geometric mean counts increasing from 330 to 95000 CFU/mL. The geometric mean of the difference was 290 CFU/mL (95% CI, 110-720 CFU/mL; P < 0.0001). No changes were noted in the xylose absorption or metabolism tests. Mean interdefecatory intervals decreased by 32% from 31.7 to 21.6 h, the mean difference being 10.1 h (95% CI, 1.6-18.5 h: P = 0.01). The mean stool form index increased from 2.95 to 4.70, mean difference 1.75 (95% CI, 1.10-2.40: P < 0.0001), with four patients reporting diarrhoea. CONCLUSIONS The results indicate that conventional treatment for duodenal ulcers with a proton pump inhibitor significantly increases bacterial colonization of the duodenum and the speed of intestinal transit.