The central effect of nicotine on gastric acid secretion was examined in rats anesthetized with urethane. Intraventricular administration of nicotine 5 and 20 microgram/animal induced a dose-related increase in acid output. This nicotine-induced increase was blocked by treatment with hexamethonium 50 microgram/animal given intraventricularly or atropine 100 microgram/kg given intravenously. Changes in acid output after intravenous administration of nicotine 100 microgram/kg were inconsistent; however, a significant increase was observed with 500 microgram/kg of this alkaloid given by the same route. This increase was also blocked by hexamethonium 50 microgram/animal given intraventricularly. The level of gastrin in the gastric juice, after the intraventricular administration of nicotine 20 microgram/animal, did not significantly differ from the control. These results suggest that nicotine administered intraventricularly stimulates nicotinic receptors in the brain, and that there is a subsequent excitation of cholinergic muscarinic receptors in the stomach after which the secretion of acid increases.