To define the optimum doses of omeprazole appropriate for acute and long-term therapy of patients with gastro-oesophageal reflux disease, 24-h oesophageal pH was measured in 12 patients with symptomatic reflux and an abnormal 24-h oesophageal acid exposure time (greater than 6%) in a randomized, double-blind, four-way crossover study comparing the effects of omeprazole 10, 20, or 40 mg/day and placebo. Total reflux time over 24 hours, number of reflux episodes per hour, and the number of reflux episodes lasting greater than 5 minutes were measured by ambulatory 24-h oesophageal pH monitoring. All doses of omeprazole were superior to placebo in decreasing gastro-oesophageal reflux as measured by each index. With placebo, oesophageal acid exposure was 16.3% of the 24 hours, 10 mg omeprazole/day reduced that to 6.3%, 20 mg/day lowered acid exposure to 0.9%, and 40 mg/day to 0.6%. Thus only the 20 and 40 mg doses reduced acid exposure to within the normal range. Similar results were obtained with the other indices of reflux. These data suggest that a rational dose regimen for reflux oesophagitis is 20 mg/day, a regimen that has proved effective in clinical trials. The present study indicates that 24-hour oesophageal pH monitoring is a practical approach to the determination of drug dosage in patients with gastro-oesophageal reflux.