Intracerebroventricular (ICV) and subcutaneous (SC) injections of sauvagine powerfully inhibited gastric acid secretion stimulated by gastric distension and by 2-deoxy-D-glucose, but not by histamine in pylorus-ligated rats. Naloxone failed to antagonize the antisecretory effects of SC and ICV sauvagine. Intravenous infusion of sauvagine completely suppressed bethanechol-stimulated gastric secretion, significantly decreased pentagastrin-stimulated gastric secretion and did not modify histamine-stimulated gastric secretion in gastric-perfused rats. The inhibitory effect of sauvagine on gastric secretory response is not mediated through opioid or histamine receptors. It appears to be dependent on a vagal mechanism as well as other mechanisms that await further elucidation.