Omeprazole, a substituted benzimidazole inhibitor of the gastric H+/K+-ATPase, is a potent and long-acting antisecretory drug. Because of its high potency and because of the possible risk of long-term hypergastrinaemia intermittent therapy with this drug may be preferable to continuous treatment in patients requiring long-term treatment. We have therefore studied the effect of weekly 3-day courses of 20 mg/day omeprazole followed by a 4-day period without medication (weekend therapy) for 4 weeks on basal and bombesin- (150 ng/kg.h) and pentagastrin- (1.5 micrograms/kg.h) stimulated gastric acid secretion in 10 normal subjects. Gastric acid was measured in week 1, before (day 1) and immediately after the 3-day omeprazole course (day 4), and further on day 6 and day 8, immediately before the next course, and at similar intervals in week 4 (days 22, 25, 27, and 29). When compared with pretreatment values, basal and bombesin- and pentagastrin-stimulated gastric acid were significantly (p less than 0.01-p less than 0.05) inhibited on the days immediately after the courses (days 4 and 25) but were, except for a significant (p less than 0.05) reduction of pentagastrin-stimulated gastric acid on day 8, not significantly affected on all other days. Basal and integrated bombesin-stimulated serum gastrin values were not significantly changed, whereas bombesin-stimulated peak serum gastrin was significantly (p less than 0.05) increased on days 22 and 29. Since this schedule of omeprazole induces pronounced, but transient, inhibition of gastric acid secretion without provoking marked hypergastrinaemia, intermittent weekend therapy may be suitable for long-term maintenance treatment with this drug.