To determine the influence of changes in gastric juice pH due to intravenous administration of pentagastrin and omeprazole on intramucosal regional PCO2 (Pr(CO2)), we investigated 17 healthy human volunteers. Gastric juice pH was obtained from a glass pH electrode for continuous gastric juice pH measurement and Pr(CO2))was measured by using automated air tonometry. After baseline (8:00 A.M.-9:00 A.M.) the subjects received 0.6 microg/kg/h pentagastrin intravenously for 1 h (9:00 A.M.-10:00 A.M., after stimulation 10:00 A.M.-11:00 A.M.) and 40 mg omeprazole intravenously (after omeprazole 11:00 A.M.-3:00 P.M.). Following pentagastrin administration gastric juice pH significantly decreased from 1.2 +/- 0.4 to 0.6 +/- 0.4 (mean +/- SD, p < 0.007, versus baseline), whereas omeprazole transiently increased luminal pH up to 4.4 +/- 1.7 (p < 0.007 versus baseline). These subsequent changes in gastric juice pH were accompanied by a significant increase in Pr(CO2) from 48 +/- 12 to 61 +/- 17 mm Hg (p < 0.007 versus baseline) and a decrease to 44 +/- 5 mm Hg (p < 0.002 versus pentagastrin), respectively. A gastric juice pH > 4 considerably reduces mean gastric Pr(CO2) and interindividual variability. Thus omeprazole may improve the validity of gastric tonometry data.