Cysteamine in a single s.c. administration induces release of gastrin, acid hypersecretion and duodenal ulcer in rats. Pentagastrin-induced acid hypersecretion has no ulcerogenic effect. The Brunner glands in the proximal duodenum were previously an important factor in the natural defense of the duodenal mucosa. The effect of cysteamine and pentagastrin on the Brunner glands in the rat was studied. The proximal duodenum was isolated in situ and drained by a polyethylene tube. The secretion was studied for two 5 h periods after administration of cysteamine or pentagastrin and then the Brunner glands were studied histologically. Pentagastrin did not affect spontaneous Brunner gland secretion, whereas cysteamine inhibited the output approximately 50%. After cysteamine the secretory cells were low and depleted of mucus, suggesting that cysteamine interferes with the synthesis of the secretory product. The depression of the Brunner gland secretion may be an important factor in the pathogenesis of cysteamine-induced duodenal ulceration.