The peristaltic reflex is elicited by a local distension of the intestine and consists of an ascending contraction and a descending inhibition of the smooth muscle layer. The transmitter mediating the inhibition of the smooth muscle cells is not known but vasoactive intestinal polypeptide (VIP) has, among others, been proposed to mediate the descending inhibition of a distension. An in vivo preparation of a segment of the feline intestine was designed to allow collection of the venous effluent and determination of the VIP release orally and anally of a distension. The release of VIP rose significantly more on the anal side of the intestinal distension, and so did the blood flow. Division of the myenteric plexus prevented the asymmetry of the VIP release to a large extent. These effects of distension on the release of VIP are consistent with the hypothesis that VIP mediates the descending inhibition of the peristaltic reflex.