The sensitivity of three breath tests (1-g [14C]xylose, 10-g lactulose-H2, and 80-g glucose-H2) was studied in 20 subjects with culture-documented small intestine bacterial overgrowth. Elevated breath 14CO2 levels were seen within 30 min of [14C]xylose administration in 19 of 20 subjects with bacterial overgrowth and 0 of 10 controls. In contrast, H2 breath tests demonstrated uninterpretable tests (absence of H2-generating bacteria) in 2 of 20 subjects with bacterial overgrowth and 1 of 10 controls and nondiagnostic increases in H2 production in 3 of 18 glucose-H2 and 7 of 18 lactulose-H2 breath tests in subjects with bacterial overgrowth. These findings demonstrate continued excellent reliability of the 1-g [14C]xylose breath test as a diagnostic test for bacterial overgrowth, indicate inadequate sensitivity of H2 breath tests in detecting bacterial overgrowth, and suggest the need for evaluation of a 13CO2 breath test having the same characteristics as the [14C]xylose test (avidly absorbed substrate having minimal contact with the colonic flora) for nonradioactive breath detection of bacterial overgrowth in children and reproductive-age women.