A physiological role for endoluminal serotonin (5-HT) was explored in in vivo experiments, where feline jejunal segments were endoluminally perfused with saline or a low concentration of 5-HT. The upper jejunal segment was initially perfused with saline, followed by 5-HT in saline, and finally perfused with saline alone. The lower jejunal segment served as a control with constant perfusion with saline. The regional blood flow to the small intestine was determined by the microsphere technique. Endoluminal perfusion with 5-HT caused a selective muscular hyperaemia of the experimental gut segment, which was normalised upon subsequent saline perfusion. The blood flow to the saline perfused control segment was unchanged. This was also the case for control tissues; that is, adjacent small intestinal regions and kidneys. The 5-HT-induced muscular hyperaemia was confined to the experimental gut segment and seems to be mediated by a local cholinergic neural mechanism, activated from the mucosa, since the hyperaemic response was prevented by muscarinic blockade or local anaesthesia applied to the luminal surface of the experimental segment. The vascular response does not seem to involve 5-HT2 receptors, since selective blockade of such receptors did not prevent 5-HT-induced hyperaemia.