We measured breath H2 excretion in 122 neonates from birth to 1 month of age. The patients weighed less than 2000 g at birth and thus were at risk for developing necrotizing enterocolitis (NEC). Hydrogen excretion was normalized for the quality of the expired air by dividing by the carbon dioxide pressure of the gas sample. The mean (+/- SD) peak H2/CO2 ratio was significantly different between the seven patients who subsequently developed NEC (9.4 +/- 2.7 ppm/mm Hg) and the 115 patients who did not (5.0 +/- 3.5 ppm/mm Hg). The prevalence of NEC was 5.7% in the present study. Defining a positive test as one with a ratio value of greater than or equal to 8.0 ppm/mm Hg, the resulting screening test had a sensitivity of 86% and a specificity of 90%. The screening test yielded a 33% predictive value of a positive test and a 99% predictive value of a negative test. High H2 excretion occurred eight to 28 hours before the earliest clinical signs of NEC. Breath H2 excretion is a simple noninvasive test that may be useful in the management of the premature neonate at risk for the development of NEC.