This review examines the evidence for the existence in the gastrointestinal tract of a new subtype (H3) of histamine receptors, previously described in the central nervous system. Study of these receptors is facilitated by the availability of the highly selective agonist (R) alpha-methylhistamine and the selective antagonist, thioperamide. H3-receptors seem to exert negative control on gastric acid secretion evoked by indirect cholinergic stimuli: their localization is unclear but it seems to be outside the parietal cell. H3-receptors also seem to be located on cholinergic and non-adrenergic non-cholinergic (NANC) neurones of the myenteric plexus, where they negatively control the release of neurotransmitters.