The problem of stress ulcer was studied clinically and in the laboratory. Ten of 19 patients comatose following severe cerebral trauma showed evidence of gastric acid hypersecretion within the first week posttrauma. Three of the ten bled briefly from presumed stress ulcer. Hypersecretion was reduced in three patients after administration of a parasympatholytic drug. Acid hypersecretion occurred both in patients with and without corticosteroid therapy. The "Cushing's ulcer" appears to differ from other forms of stress ulcer in having a higher incidence of associated gastric hyperacidity. Neostigmine bromide, pilocarpine hydrochloride, vitamin A, and phytohemagglutinin failed to stimulate mucus secretion when used topically in gastric pouches. The concept of a topical mucigogue for use in stress ulcer patients remains to be established.