Sixty-two patients with healed duodenal or prepyloric ulcers completed a double-blind long-term trial with either 25 mg/day of trimipramine (32 patients) or placebo (30 patients). Endoscopy was performed when marked dyspeptic complaints occurred or after a 1-year follow-up study. Eleven patients in the trimipramine-treated group and 18 patients in the placebo group had relapses, with endoscopically confirmed ulcers or erosions with duodenitis and severe symptoms, revealing a statistically significant difference between the groups in favour of trimipramine. Twenty-one patients (66%) receiving trimipramine and 12 patients (40%) receiving placebo were in remission at the end of the study. The probability of having a relapse increased with the time from start of placebo but decreased in the group that received trimipramine. No serious side effects occurred. In conclusion, 25 mg of trimipramine daily reduced significantly the recurrence rate of duodenal ulcer disease, when compared with placebo.