The release of secretin into plasma by intraduodenal (id) infusion of HC1 or iso-osmotic (290 mosm l_1) NaCl, and the associated changes of moderately stimulated gastric acid, serum gastrin, two calciotropic hormones, total and 45calcium (Ca), were examined in the rat. The possible role of endogenous secretin as an enterogastrone and as a mediator of the hypothesized endocrine gut-thyroid-parathyroid axis was further characterized with the aid of secretin immunoneutralization and exogenous secretion. The id-HCI-stimulated secretin, measured by a sensitive radioimmunoassay, was accompanied by a decrease in gastric acid secretion, whereas secretin blockage by