Galanin was present and exerted potent effects in all the gastrointestinal sphincters examined. Galanin-immunoreactive nerve fibers and neurons are present in both the myenteric and submucosal plexuses of sphincters. The neuropeptide exerts diverse effects in different sphincteric smooth muscles that may be species specific. For example, in the lower esophageal sphincter, it may cause an increase in basal tone and suppression of nonadrenergic noncholinergic (NANC) nerve-mediated relaxation. On the contrary, in the internal anal sphincter (IAS), the predominant effect of galanin is to cause smooth muscle relaxation and augmentation of NANC nerve-mediated relaxation. In other sphincters, galanin may either have no effect or cause either an increase or a decrease in basal tone. Most of the actions of galanin on basal smooth muscle sphincteric tone are due to its actions directly on smooth muscle cells. However, some of the relaxant actions of the peptide may also be due to activation of NANC inhibitory neurons. The basic mechanism/s responsible for sphincteric smooth muscle contraction or relaxation in response to galanin have not been investigated. The suppressive as well as the augmentatory effects of galanin on NANC nerve-mediated sphincteric smooth muscle relaxation may be due to inhibition or facilitation, respectively, of the release of NANC inhibitory neurotransmitters such as nitric oxide and vasoactive intestinal polypeptide. Diverse effects in different gastrointestinal sphincters suggest a neuromodulatory rather than a neurotransmitter role of galanin and a significant role of the neuropeptide and putative antagonists in the pathophysiology and potential therapy of gastrointestinal motility disorders especially those affecting sphincteric function.