The mechanism and time for healing of cysteamine-induced duodenal ulcers in rats were investigated. Cysteamine induces a mixture of erosions, ulcers, and penetrating ulcers. These three stages of ulcerations healed in different ways and in different times. Erosions healed within three days by formation of new mucosa from the epithelium of the remaining parts of the crypts of Lieberkühn. The mucosa became completely normal within 15 days. Ulcers healed primarily by a contraction of the circular layer of the external muscle coat, thereby approaching the ulcer edges and reestablishing a complete layer of Brunner's glands in the submucosa. Healing was complete within 15 days. Penetrated ulcers healed very slowly by formation of new epithelium and Brunner's glands from the ulcer edges. The newly formed epithelium was desquamated unless protected by underlying Brunner's glands and the regeneration of these therefore determined the healing of the ulcer. Only a few of these ulcers had healed after 50 days. After 100 and 150 days, approximately 50% had healed, and after 200 days still only 64% had healed. Thus the cysteamine ulcer with destroyed muscle coat has a very prolonged healing and thereby represents a model for a chronic duodenal ulcer which may be of value as a model for testing treatments of duodenal ulcers.