There is a lack of information about the effectof omeprazole or other antisecretory drugs onintraduodenal pH. Aim of the study was to document thevariation over time of intraduodenal pH during a 24-hr period and to simultaneously study the effectof omeprazole 40 mg once daily on intragastric andintraduodenal pH in healthy H. pylori-negative subjects.In a randomized, placebo-controlled study, eight subjects (five women, three men, mean age 22.7years) received oral 40 mg omeprazole or placebo oncedaily for eight days. On day 7, intragastric andintraduodenal pH was measured continuously for 24 hr, using two miniature glass-membrane electrodesplaced in the stomach (fundus) and in the distal thirdof the duodenum. The 24-hr median intraduodenal pH was5.95 with placebo and 5.85 with omeprazole. Median intragastric pH was 1.68 without and 4.93 withomeprazole. During omeprazole therapy, intragastric pHfell below 4.0 in five of eight subjects. In the 2- and3-hr postprandial periods, the percentage of time with pH < 5 was significantly reducedwith omeprazole. In healthy subjects, 24-hr median andpostprandial pH in the distal part of the duodenum waslower than previously thought. Omeprazole significantly reduced the percentage of time with pH < 5postprandially. At night, intragastric pH fell below 4.0with omeprazole 40 mg once daily. Omeprazole does notchange 24-hr median intraduodenal pHsignificantly.