Background: Nocturnal gastric acid breakthrough is defined as night-time periods when gastrin pH falls below 4.0 for greater than Ih during administration of a proton pump inhibitor, This phenomenon is a serious problem for patients who require strict control of their gastric acid secretions. Aim: To investigate the prevalence of nocturnal gastric acid breakthrough in Japanese subjects during administration of rabeprazole, and to clarify the relationship between Helicobacter pylori infection and nocturnal gastric acid breakthrough Methods: Thirty-one normal male volunteers were examined by ambulatory 24 h gastric pH monitoring four times: without medication, after a morning or an evening dose of 20 mg rabeprazole, and after administration of an H-2-receptor antagonist at bedtime, in addition to the morning dose of rabeprazole, a pylori infection was determined by the C-13-urea breath test and an assay for serum anti-a pylori antibody, Result: Nocturnal gastric acid breakthrough was observed in 12 patients (39%) after the morning dose of 20 mg rabeprazole. In all cases, nocturnal gastric acid breakthrough was inhibited completely by administration of the H-2-receptor antagonist at bedtime, Only one patient with nocturnal gastric acid breakthrough had a pylori infection. Conclusion: The absence of a pylori infection appears to be closely related to the occurrence of nocturnal gastric acid breakthrough during dosing with a proton pump inhibitor.