The purpose of the present study was to evaluate whether the inhibitory effects of beta-adrenergic agonists on gastric secretory activity in vivo could be mediated through a local release of somatostatin. The gastric secretion was measured during continuous stimulation with pentagastrin (1 microgram/kg/h). The infusion of isoprenaline (beta 1 + beta 2), salmefamol (beta 2), and somatostatin produced inhibitory effects on both acid and pepsin secretion. The reaction patterns were similar for isoprenaline and somatostatin, whereas salmefamol induced an inhibition of longer duration and with dissimilar dose-response kinetics. The gastric somatostatin release was significantly increased after infusion of both beta-adrenergic agonists and somatostatin, with patterns similar to those obtained for the secretory inhibition. There was a significant correlation between the somatostatin release and the acid and pepsin secretion during infusion of the secretory inhibitors but not in the control state. This study shows that beta-adrenergic agonists have inhibitory effects on gastric secretion in vivo similar to those of somatostatin. Both somatostatin and the beta-adrenergic agonists stimulated the release of somatostatin from the gastric mucosa. beta-Adrenergic antagonists were without effects. Somatostatin thereby fulfils the requirements for an endogenous mediator of the beta-adrenergic inhibition.