Vasoactive intestinal polypeptide (VIP) is a 28 amino acid with a wide-spread neuronal localization. VIP fulfils many of the classical criteria for neurotransmission. In the cerebral cortex bipolar VIP neurones are involved in the coupling between energy metabolism, blood flow and neuronal activity. Furthermore, VIP in the brain plays a role in circadian rhythms and melatonin and pituitary hormone secretion. In the peripheral nervous system VIP is the transmitter of a number of non-cholinergic, non-adrenergic autonomic events. Thus, the peptide is involved in the control of smooth muscle tone and motility, blood flow and secretion in the digestive tract, respiratory tract and urogenital tract. The effects of VIP are mediated by a specific membrane-bound receptor linked to adenylate cyclase via a stimulatory G-protein. It is likely that impairment of VIP nerves is involved in some autonomic dysfunctions, an example being male impotence which is successfully treated with VIP injections.