Summary ACTH administered intramuscularly to normal subjects in doses of 100-160 mg daily for periods of 3-4 weeks produced a marked increase in the basal gastric secretion of hydrochloric acid and pepsin associated with an equally significant rise in the urinary uropepsin excretion. In every instance these values were increased to the levels usually observed in patients with active peptic ulcer. These studies indicate that an endocrine relationship exists between the stomach and the adrenal gland and that a hormonal phase of gastric secretion may be mediated by the adrenal corticoids. The pathway by which chronic emotional and physical stress may affect the stomach by a hypothalamus-pituitary-adrenal-gastric pathway is discussed.