The effect of the substituted benzimidazole omeprazole on acid secretion after repeated administration to healthy volunteers has been studied. During repeated dosage of 30 mg once daily inhibition of basal and pentagastrin-stimulated acid output was increased from 30% after the first dose to about 60% after dose 4. The extent of inhibition did not further increase between day 5 and day 10. In four volunteers acid secretion returned to predose levels within 5 days after drug withdrawal. The 24-hour gastric acidity was reduced by about 72% and 82% after 9-day pretreatment with 30 mg and 60 mg omeprazole respectively. The antisecretory effect of omeprazole was independent of peak plasma concentrations. Omeprazole given once daily therefore possesses a long-lasting effect on gastric acid secretion, i.e. for more than 24 hours. This effect appears to be fully reversible since control levels of acid output are reached within 5 days.