Saliva is a neurally induced solution with buffering capacity against acidic solutions. Salivation therefore plays an important role in defending the esophageal mucosa against refluxed gastric acid and is evoked by cholinergic stimulation. Both nizatidine and cisapride are reported to increase acetylcholine concentrations in the postganglionic cholinergic synapses. We performed this study to clarify the effect of administration of nizatidine and cisapride on salivary secretion. Eight-week-old male Sprague-Dawley rats were used for the experiments. Histamine-stimulated gastric acid secretion was measured after intraduodenal administration of nizatidine or famotidine to determine the equipotent acid-suppressing doses. Salivary secretion was then measured for 3 hr after intraduodenal administration of nizatidine (30 mg/kg), famotidine (3 mg/kg), or cisapride (1 mg/kg). Both nizatidine and famotidine dose-dependently inhibited histamine-stimulated gastric acid secretion. Total salivary secretion was significantly increased by nizatidine (P = 0.02) and cisapride (P = 0.02) but not by famotidine (P = 0.50) compared with controls.