1. The release of vasoactive intestinal polypeptide (VIP) into venous blood from the small intestine of the cat was studied when mechanically stimulating the intestinal mucosa and during close intra-arterial infusions of 5-hydroxytryptamine (5-HT) or isopropylnoradrenaline. The studies were performed on anaesthetized cats given atropine.2. Mechanical stimulation of the intestinal mucosa induced a vasodilatation and a release of VIP into the intestinal venous blood. Intra-arterial administration of tetrodotoxin was given in doses that blocked the vasoconstrictor effect of the regional sympathetic nerve fibres. This also abolished the vascular response and the release of VIP into blood upon mechanical stimulation.3. Close intra-arterial administration of 2-bromo-lysergic acid diethylamide reduced the VIP release and the intestinal vasodilatation upon mucosal stimulation to largely the same extent.4. Close intra-arterial infusions of 5-HT produced a marked release of VIP from the intestine and a moderate vasodilatation. Close intra-arterial infusions of isopropylnoradrenaline, which caused a pronounced intestinal vasodilatation, evoked only a small release of VIP.5. The results are compatible with the hypothesis that the vasodilatation in the gut, induced by mechanical mucosal stimulation, is mediated via an intramural nervous reflex containing a neurone capable of releasing VIP. It is proposed that the nervous reflex is activated by the release of 5-HT from the enterochromaffin cells evoked by mechanical stimulation of the mucosa.