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To evaluate and further characterize duodenal ulcer healing macroscopical, histological, and ultrastructural criteria were examined in 24 patients with active duodenal ulcer disease under two different treatment schedules. After the endoscopic confirmation of an active duodenal ulcer patients were randomly assigned to treatment with either an antacid (group A) or with an H2 blocker (group B). Tissue specimen were taken during endoscopy from the margin and 1 cm from the ulcer before therapy and from the ulcer scar or the previous ulcerated region after a 4 week treatment. A macroscopic ulcer healing by endoscopic criteria was confirmed in 83% of the patients in group A and in 83% of group B. The prominent histological feature of duodenal ulcer healing was a significant increase of PAS positive epithelial cells. Ultrastructural changes of the duodenal mucosa were still present at the end of the treatment, even in the presence of complete macroscopic healing. The ultrastructural healing process shows constant patterns independent from the type of treatment. The characteristic morphological feature by electron microscopy of the healing duodenal ulcer is the appearance of a metaplastic mucus secreting cell of the antrum-type. The devastated mucous structure during the ulcerative phase regains the normal net-like structure after 4 weeks therapy.