Objective: To test our standard dosing regimen in omeprazole treatment of gastrooesophageal reflux disease (GORD) and to determine whether 'non-responders' could be pinpointed. Design: A reverse dose-response examination using increasing doses of omeprazole. The study was conducted as an open consecutive clinical study. Response was measured by 24-h pH-metry, symptoms, endoscopy and histopathology. Setting: All patients had been referred to one of the partaking departments for evaluation of oesophageal reflux symptoms. Patients: A total of 62 patients were included, 29 with systemic sclerosis and 33 consecutively included patients suffering from idiopathic oesophageal reflux. Results: Approximately one-third of the patients required doses higher than 40 mg of omeprazole/day (up to 140 mg/day) to abolish GOR. No cases of tachyphylaxia or bile-induced oesophagitis were seen in this study. In all patients subjected to dose titration we were able to achieve healing of oesophagitis assessed by symptom scoring, endoscopy and histopathology. No prediction of final dose of omeprazole could be made. Conclusion: Four weeks after reaching a dose level of omeprazole that ensured the abolition of GOR, healing of oesophagitis according to endoscopic/histological evaluation was obtained in all patients. Persistent oesophagitis, i.e. bile induced, was not found.