The central nervous system effects of thyrotropin-releasing hormone (TRH) on gastric acid secretion and mucosal blood flow were studied in rats. Corpus mucosal blood flow was measured by the hydrogen gas clearance technique and acid output by a continuous gastric perfusion method in fasted, urethane-anesthetized rats. Thyrotropin-releasing hormone (1 or 5 micrograms) injected into the cerebral lateral ventricle induced concomitant increases in gastric acid secretion and mucosal blood flow. Intravenous infusion of step doses of TRH (60 and 180 micrograms/kg.h) had no effect on these parameters. Bilateral vagotomy and atropine (0.15 mg/kg) completely blocked the effects of intracerebroventricular injection of TRH (5 micrograms) on gastric acid secretion and mucosal blood flow. In contrast, intravenous omeprazole (20 mumol/kg) completely inhibited the increase in gastric acid secretion but not the increase in mucosal blood flow elicited by intracerebroventricular administration of TRH (5 micrograms). These results demonstrate that TRH acts in the brain to stimulate gastric acid secretion and mucosal blood flow through vagal dependent pathways and peripheral muscarinic receptors. Part of the effect of central TRH on gastric mucosal blood flow is not secondary to the stimulation of acid secretion and appears to represent a direct cholinergic vasodilatory response.