Isoproterenol (Iso), epinephrine and norepinephrine each stimulated isolated gastric mucosal parietal cells as shown by an increased accumulation of [14C]aminopyrine (AP), an indirect measure of acid secretion. The beta receptor selective agonists metaproterenol, terbutaline and zinterol stimulated AP accumulation to the same extent as Iso, whereas the beta-1 receptor selective agonist dobutamine was only 20% as effective. The general beta receptor antagonists oxprenolol and dl-propranolol and the beta-2 receptor antagonist H35/25 inhibited Iso-stimulated AP accumulation. Receptor stereoselectivity was shown by the approximately 100-fold difference in potency of the I- and d-isomers of propranolol. The alpha receptor antagonists phentolamine and phenoxybenzamine, the beta-1 receptor antagonists metoprolol and practolol and the muscarinic receptor antagonist atropine were without effect. The histamine H2-receptor antagonist cimetidine inhibited Iso-stimulated AP accumulation an average of 40% at a concentration which inhibits completely histamine-stimulated AP accumulation. The data demonstrate that cells of the rat gastric mucosa have adrenergic beta-2 receptors which when stimulated result in an increase in acid secretion. The results also show that the response is in part mediated indirectly by catecholamine-stimulated release of histamine.