A major part of the net fluid secretion that is elicited by cholera toxin in the small intestine of the cat has been shown to be mediated by intramural nervous reflex(es). The release of vasoactive intestinal polypeptide (VIP) from the small intestine is increased by cholera toxin. We report that close intra-arterial infusions of methionine-enkephalin (met-enk) and somatostatin cause a parallel reduction in cholera toxin-induced net fluid secretion and in VIP release from the small intestine of the cat. Intestinal blood flow was slightly, but significantly increased by met-enk and not influenced by somatostatin. These results strengthen the hypothesis that VIP is involved as a neurotransmitter in the nervous reflex mediating cholera toxin-induced secretion.