Background: We evaluated the clinical utility of the C-13-xylose breath test for the diagnosis of small bowel bacterial overgrowth in children. Methods: To determine the optimal dose of C-13-xylose, 29 healthy children, 3 to 12 years old, were randomly assigned to receive one of three doses of C-13-xylose (10, 25, or 50 mg). After an overnight fast, the oral dose of C-13-xylose was administered, and breath samples were collected every 30 minutes for 4 hours. Samples were analyzed for (CO2)-C-13 by gas chromotography with mass spectrometry. Using the 50 mg dose, we then performed nine breath tests with concurrent duodenal bacterial cultures in 6 children, 3 to 12 years old, with short-bowel syndrome (n = 2), immunodeficiency states (n = I), and motility disorders (n = 3). Results: Excretion of (CO2)-C-13 in breath peaked at 2.5 hours in all three control groups. The 50-mg dose produced the highest median peak and the smallest range of (CO2)-C-13 excretion in breath within each time period. The time of peak (CO2)-C-13 excretion in breath varied among the diseased children; however, the six patients with small-bowel bacterial overgrowth (2 x 10(5) - 3.5 x 10(8) gram negative rods) all had peak (CO2)-C-13 that exceeded the maximum breath (CO2)-C-13 level in breath of the control subjects at the corresponding time period (100% sensitivity). Of the three patients with negative cultures, two had negative breath test results and one had positive results (67% specificity). One subject had normalization of both duodenal culture and breath test results after antibiotic treatment of small-bowel bacterial overgrowth. Conclusions: Our preliminary results suggest that with a dose of 50 mg C-13-xylose, breath test results reliably predict small-bowel bacterial overgrowth in susceptible children.