Lansoprazole is a potent proton pump inhibitor and blocks gastric acid secretion. The potency of many antibiotics in eradicating Helicobacter pylori may be considerably enhanced by increasing the intragastric pH due to a twice-daily coadministration of proton pump inhibitors. This double-blind crossover study was designed to compare the effect on intragastric pH of four dose regimens of lansoprazole (30 mg o.a.d., 30 mg b.i.d., 45 mg b.i.d., 60 mg b.i.d.) after 5 days of treatment and to investigate whether an increment of lansoprazole dose level leads to a more pronounced effect. Omeprazole 20 mg b.i.d. was administered as a reference drug. The study was carried out in 20 healthy male subjects. Intragastric pH was recorded by a nasogastric probe over 24 h. All dose regimens of lansoprazole were well tolerated and no unexpected drug-related adverse events were observed. The lowest lansoprazole dose level, 30 mg o.a.d. already increased intragastric pH considerably. This effect was even enhanced by increase of the lansoprazole dose as assessed by mean pH as well as percentage of time spent above different pH values. The increase in effect with lansoprazole dose increment from 30 mg b.i.d. to 60 mg b.i.d. was only very small. The time spent at pH values above or equal to 3 after b.i.d. administration was slightly higher with all lansoprazole dose levels compared to omeprazole. The time spent at intragastric pH values above or equal to 5 after b.i.d. oral administration of 30 mg, 45 mg and 60 mg lansoprazole was comparable to that observed after b.i.d. oral administration of 20 mg omeprazole, so that it may be recommended to use lansoprazole 30 mg b.i.d. as a treatment equivalent to omeprazole 20 mg b.i.d. for eradication of Helicobacter pylori in combination with antibiotics.