The smooth muscles of the gastrointestinal tract and blood vessels are innervated by nonadrenergic, non-cholinergic (NANC) inhibitory neurons. The transmitter (s) in relation to NANC inhibitory neurons remains unknown, but there are two main working hypotheses, the purinergic and VlPergic nerve hypotheses, at present. Although there is a large amount of data supporting the purinergic hypothesis, definitive evidence is still lacking. VIP seems to be regarded as a likely candidate for the neurotransmitters of some NANC inhibitory neurons. However, the data presented are still incomplete. For the purinergic hypothesis, the discrepancies seem to be greater in the stomach and oesophagus and those for the VlPergic hypothesis, in the guinea pig taenia coli. Moreover, there are many examples of the co-existence of peptides or of peptides and synthesizing enzymes of amines or acetylcholine in the gastrointestinal tract. Therefore, it is possible that NANC inhibitory neurons liberate more than one active inhibitory substance and/or there are different types of NANC inhibitory neurons in the gastrointestinal tract. Much more evidence seem to be needed before the neurotransmitter (s) of NANC inhibitory neurons in the gastrointestinal tract and blood vessels can be identified.