Abstract Background & Aims : Acid has been shown to stimulate calcitonin gene-related peptide (CGRP) release from peripheral sensory afferent nerve endings in the stomach. The aim of this study was to determine whether endogenous CGRP was involved, by a neurocrine mechanism, in acid-mediated stimulation of somatostatin and inhibition of gastrin release. Methods : A two-compartment sleeve of antral mucosal/submucosal tissue was perfused to determine sensory nerve and endocrine cell responses to luminal acid. CGRP receptor antagonist, CGRP 8–37, was used to inhibit the actions of endogenously released CGRP. Results : Perfusion of the antral sleeve lumen with media of increasing hydrogen ion concentration caused pH-dependent increases in CGRP and somatostatin release and decrease in gastrin release. CGRP 8–37 inhibited significantly basal somatostatin (−36%) and stimulated basal gastrin (+65%) release ( P < 0.02). Furthermore, CGRP 8–37 administration prevented luminal acid-mediated inhibition of gastrin release and stimulation of somatostatin release. These results indicate that CGRP 8–37 prevented acid-mediated feedback inhibition of gastrin release and acid-induced feedforward somatostatin release. Conclusions : These results suggest that CGRP plays an important role in the response of antral D and G cells to luminal acid and that local effector action of endogenous CGRP participates in regulation of antral regulatory peptide secretion.