The efficacy and safety of mifentidine 20 mg at night, a new, potent, long-acting H2-receptor antagonist, has been compared with ranitidine 300 mg at night in 60 patients with acute duodenal ulcer, in a randomized double-blind study. Antacid tablets were allowed as additional treatment for pain relief. The treatment lasted for 4 weeks. After 4 weeks of treatment the healing rate was similar; amongst the patients who completed the treatment, healing was 68% for mifentidine, 63% for ranitidine, and on intention-to-treat analysis, healing in both groups was 63%. Pain relief and antacid consumption were similar in both groups. Clinically significant adverse effects were not detected and any changes in laboratory values were minimal, clinically insignificant and reversible. Mifentidine appears to be an effective and safe once-a-day treatment for acute duodenal ulcer disease.