Treatment of duodenal ulcer with the histamine H2-receptor antagonist, ranitidine, was assessed in a double-blind, randomized, multicenter trial in which patients were treated for two consecutive 4-week periods with ranitidine 150 mg b.i.d. or a placebo. All patients were allowed to take antacids as necessary for symptoms. Three hundred eighty-two patients were entered and 355 completed the first 4-week trial period. Ranitidine significantly improved healing at 2 weeks (37 versus 19%, p < 0.01) and at 4 weeks (73 versus 45%, p < 0.01), with better relief of pain and lower use of antacids. In the second 4-week trial period, 124 unhealed patients from the first 4 weeks were re-randomized. Ranitidine treatment resulted in a greater healing rate regardless of previous treatment (p < 0.05). In this trial, side effects were uncommon and not different between placebo and the tested drug. One case of hepatitis in the ranitidine treated group was presumed on the evidence to be non-A non-B. Ranitidine is effective and appears to be safe in the treatment of duodenal ulcer and its symptoms.