Regional administration of VIP elicited a dose-dependent relaxation of the feline sphincter of Oddi and gall-bladder. Relaxatory motor responses of these regions at efferent electrical stimulation of the vagal nerves were unmasked after atropine (resistant to propranolol but sensitive to hexamethonium). These findings in combination with the presence of a rich VIP-ergic innervation, including intrinsic VIP neurons, have made VIP a tentative post-ganglionic non-adrenergic, non-cholinergic neurotransmitter to these regions. The relaxatory motor responses elicited by VIP or vagal activation were selectively antagonized using regional administration of specific VIP antisera in support of this hypothesis.