An unusual gastropathy with submucosal glands and cysts, usually associated with muncus-secreting cell hyperplasia of the mucosa, was observed at autopsy in 11 (52%) of 21 rhesus monkeys (Macaca mulatta), but in none of nine squirrel monkeys (Saimiri sciureus). In most instances, the gastric lesion occurred spontaneously, in contrast to similar lesions in monkeys of the genus Macaca reported by other investigators, which usually were attributed to known exposure to irritants. Evidence in this dtudy and in the literature suggests that the gastric mucosa of the rhesus monkey is highly reactive to nonspecific irritants. The simian gastropathy sometimes resembles an infrequently observed gastric lesion in man, reported as diffuse heterotopic cystic malformation, and is analogous to the intestinal entity, also occuring in man, known as colitis cystica profunda.