The aim was to determine the role CGRP and/or tachykinins released from sensory neural mechanisms in enteric neural vasodilator pathways. These pathways project through the myenteric plexus to submucosal vasodilator neurons. Submucosal arterioles were exposed in the distal portion of an in vitro combined submucosal-myenteric guinea pig ileal preparation and dilation was monitored with videomicroscopy. Vasodilator neural reflexes were activated by gently stroking the mucosa with a fine brush or by distending a balloon placed beneath the flat sheet preparation in the proximal portion. Dilations evoked by mucosal stroking were inhibited 64 % by the CGRP 8-37 and 37 % by NK₃ (SR 142801) antagonists. When the two antagonists were combined with hexamethonium only a small vasodilation persisted. Balloon distention evoked vasodilations were inhibited by NK₃ antagonists (66%) but were not altered by CGRP 8-37. In preparations where myenteric descending interneurons were directly activated by electrical stimulation, combined application of CGRP 8-37 and the NK antagonists had no effect. Stimulation of capsaicin sensitive nerves in the myenteric plexus did not activate these vasodilator reflexes. These findings suggest that mucosal-activated reflexes result from the release of CGRP and tachykinins from enteric sensory neurons. Distention-evoked responses were significantly blocked by NK₃ antagonists suggesting stretch activation of myenteric sensory neurons release tachykinins which activate NK₃ receptors on myenteric vasodilator pathways.