The effects of intracranial pressure on gastric acid secretion were studied in 30 rabbits. Intracranial pressure was increased in a graded and controlled fashion using a barostat connected to a cannula in the lateral cerebral ventricle. Eighteen rabbits were studied under urethane anesthesia with a background subthreshold intravenous infusion of bethanechol. Twelve rabbits were studied in the conscious state. Increases in intracranial pressure led to immediate and significant increases in gastric acid output in a dose-related manner in both conscious and anesthetized animals. Serum gastrin levels did not increase in either group of animals. Vagotomy only partially abolished the increase in acid outputs seen with increased intracranial pressure, whereas atropine completely blocked the response. We conclude that increased intracranial pressure causes stimulation of acid secretion by a gastrin-independent cholinergic mechanism that is only partially mediated by the vagus.