SUMMARYTo determine the effect of three times daily dosing with intravenous omeprazole on intragastric acidity, 24 h intragastric pH was measured continuously with a monocrystalline antimony electrode system in 11 patients with inactive duodenal ulceration during fasting conditions. After a baseline investigation, two different dosage regimens of intravenous omeprazole were compared in a double‐blind crossover study, with regard to their ability to keep the pH ≥ 4 for as long as possible. Success in the individual patient was defined as pH ≥ 4 for at least 90% over the 24‐h period. Two doses of omeprazole [40 mg t.d.s. (120 mg) and 80 mg + 40 mg + 40 mg (160 mg)] were compared.Omeprazole (120 mg) increased the median of individual median intragastric 24‐h pH from 1.49 to 6.67. The pH was ± 4 for ≥ 90% of the 24 h in three of the 11 patients. With omeprazole, 160 mg (a loading dose of 80 mg), the median of individual median intragastric 24‐h pH increased to 7.33. The pH was ≥ 4 for ≥ 90% of the 24 h in seven of the 11 patients. Median time to reach pH 4 was 39 min after 40 mg and 20 min after 80 mg omeprazole.An initial loading dose of 80 mg omeprazole seems preferable to 40 mg to achieve a fast and sustained increase in intragastric pH to above 4 in t