<i>Background:</i> Conventional techniques for measuring gastric acidity have demonstrated the decrease in gastric acidity produced by proton pump inhibitors (PPI); however, such techniques do not detect transient or localized pH changes which may modify the intragastric environment without affecting the therapeutic efficacy of PPIs. <i>Aim:</i> To investigate local and temporal variations in intragastric pH and to test the hypothesis that omeprazole produces prolonged, generalized gastric anacidity (pH >6). <i>Methods:</i> A single-blind study was conducted with triple-point 24-hour gastric pH-metry on days 7, 14 and 21 in 14 healthy, <i>Helicobacter pylori-</i>negative volunteers (7 M; 20–46 years) who received placebo for 7 days, followed by omeprazole 20 mg daily for 14 days. <i>Results:</i> Omeprazole increased the median 24-hour pH significantly in the distal corpus (placebo: 1.3 (95% CI 1.1 to 1.6); omeprazole week 1: 4.0 (2.6–5.0); omeprazole week 2: 4.0 (2.8–4.6)) and at all other gastric recording sites (p < 0.01). At both corpus sites, nocturnal pH was lower and mealtime pH was higher than the non-meal daytime pH during placebo and both omeprazole administration periods; in the antrum, however, the major difference noted was that meal-time pH was higher than non-meal daytime pH. Antral pH was lower during meals and higher at night than proximal corpus pH. During placebo, gastric pH >6.0 was observed at 1 site only for 1.7% (median; 95% CI 0.4–3.3%), at 2 sites simultaneously for 0.24% (0.0–1.0%) and at 3 sites for 0.0% (0.0–0.28%), respectively, of the recording periods; during the second week of omeprazole, the equivalent results were 7.7% (1.4–14.0%), 4.9% (0.21–15.7%) and 4.7% (0.0–9.9%), respectively. <i>Conclusions:</i> Omeprazole, 20 mg daily, does not produce gastric anacidity despite significant increases in median 24-hour pH values. The time-, meal- and site-related variations in gastric pH observed under normal physiological conditions are seen to persist, with prolonged periods of low pH throughout the stomach and preservation of the normal, meal-related rise and nocturnal fall in gastric pH during omeprazole administration.