The effect of cimetidine (400 mg at night) and of low-dose antacid (400 mg of aluminum hydroxide plus 400 mg of magnesium hydroxide four times a day) given alone or in combination was assessed in a double-blind double-dummy endoscopic trial on prevention of duodenal ulcer (DU). Seventy-five outpatients with healed DU were followed up clinically for 1 year and were checked endoscopically after 6 and 12 months of therapy or in case of symptomatic relapse. After 6 and 12 months, 25% and 41%, respectively, of patients treated with cimetidine alone experienced a relapse, compared with 42% and 54% of those treated with antacid alone and 25% and 43% of patients treated with the combination therapy. The differences are not statistically significant. No relevant side effects were observed in patients of any group. It is concluded that long-term prophylactic treatment of DU with low-dose antacid is as safe and effective as cimetidine treatment, whereas a combination of the two drugs does not achieve a therapeutic gain.