Maintenance of adequate perfusion is essential for health of the intestinal mucosa. Methods available to assess intestinal perfusion provide information on mesenteric blood flow, which may differ from mucosal flow. Intramucosal pH (pH(i)) is influenced by tissue oxygenation and perfusion. Gastric pH(i) can be measured using the technique of tonometry. A prospective observational clinical study was performed to examine relationships between measured gastric pH(i) and mucosal CO(2) (mCO(2)), and acid-base balance, gastrointestinal complications (necrotizing enterocolitis and perforation), and death in infants <1500 g birth weight. A nasogastric tonometry catheter (size 5F) was inserted into the stomach of infants, and pH(i) was calculated from mCO(2) levels measured using saline tonometry. Measurements were performed at 3, 12, 24, and 48 h, then daily until arterial access was unavailable. Two hundred eleven sets of measurements were performed on 38 infants [birth weight (mean +/-SD), 863 +/- 241 g; gestation, 26.5 +/- 1.8 wk; and median Clinical Risk Index for Babies score, 8.0 (interquartile range, 5.0-10.75)]. Mean pH(i) was 7.27 (95% confidence interval, 7.26-7.28) and mean mCO(2) was 47.0 mm Hg (95% confidence interval, 45.7-48.3 mm Hg). pH(i) and mCO(2) correlated significantly with arterial pH (pH(a)), arterial PCO(2) (PaCO(2)), and arterial base excess. There were no significant relationships between pH(a) and pH gap (pH(a)-pH(i)) or CO(2) gap (mCO(2)-PaCO(2)). Recurrent low pH(i) (<7.2 on more than one occasion) and an mCO(2)/PaCO(2) ratio of > or =1.29 were significantly associated with an increase in gastrointestinal complications. There were no statistically significant associations with death. In conclusion, changes in pH gap and CO(2) gap can occur without alteration in pH(a). Abnormalities in pH(i) might predict gastrointestinal complications in infants <1500 g.