Publisher Summary The vasoactive intestinal peptide (VIP) was so named because of its isolation from the intestinal extracts and the potent vasodilator activity that guided its purification. The highest concentrations of VIP in the central nervous system are found in the cerebral cortex, suprachiasmatic nucleus, anterior olfactory nuclei, bed nucleus of stria terminalis, medial preoptic nucleus, nucleus accumbens, amygdala, striatum, hippocampus, central gray of the midbrain, and sacral spinal cord. VIP is a 28-amino-acid residue peptide that is structurally related to at least nine other peptides; together, they may be considered to belong to one of the several identifiable families of peptides. VIP-related peptides include peptide histidine isoleucine (PHI), peptide histidine methionine (PHM), secretin, glucagon, corticotropin-releasing factor (CRF), growth hormone-releasing factor (GRF), sauvagine, urotensin I, helodermin, and gastric inhibitory peptide (GIP). The structural features in common among these peptides account for some similarities that they exhibit in certain biological actions and some overlap in the binding to certain receptor sites. The structure of VIP is relatively well conserved through the animal kingdom. VIP has biological activity on a wide variety of organ systems and body functions, including central and peripheral neurons, and digestive, cardiovascular, respiratory, reproductive, exocrine, endocrine, neuroendocrine, immunologie, and renal functions. VIP is an important mediator or modulator of several basic physiological events, including the relaxation of vascular and nonvascular smooth muscle and the stimulation of water, electrolyte, macromolecular, and certain endocrine and neuroendocrine secretions.