Ten Argentine centers participated in this cooperative trial. One hundred and sixteen patients with endoscopically proven duodenal ulcer entered the study and were randomly assigned to receive either Misoprostol 800 micrograms or Cimetidine 1200 mg, q.i.d. per day, during four weeks of treatment. Patients were allowed to take Amphogel tablets for relief of ulcer pain when necessary, and clinical, lab-tests and adverse effects were evaluated weekly. Ninety-nine patients (Misoprostol 54, Cimetidine 45) completed the study and were evaluable. Success/failure criteria were based on endoscopically documented complete healing at the end of treatment period. Healing rate of four week was 85.2 per cent (46/54) for Misoprostol and 75.5 per cent (34/45) for Cimetidine, with no statistically significant difference. It is concluded that Misoprostol and Cimetidine are highly effective and safety in the healing of active duodenal ulcer. Misoprostol is a new therapeutical alternative for the treatment of duodenal ulcer patients.