The histologic and ultrastructural features of a time sequence study of the development, evolution, and healing of acetic acid-induced experimental duodenal ulcer are presented. Duodenal ulcers produced by serosal application of acetic acid featured microvascular injury with progressive disintegration of the tips of the mucosal villi and subtotal necrosis of the duodenal wall. At 3 days ulcers transformed into a chronic state with regenerating epithelium originating from the crypts of the intact bordering mucosa extending toward the center of the ulcers. By 21 days healed ulcers were covered by distorted duodenal surface mucosa. We conclude that this reproducible and standardized model of duodenal ulcer features vascular injury as the earliest microscopic event, that ischemic necrosis leads to ulceration, and that the chronic phase bears morphologic resemblance to human duodenal ulcer.