The exquisite specific excitatory and desensitising actions of capsaicin on a subpopulation of primary sensory neurons have been instrumental in identifying the roles of these neurons in nociception, reflex responses and neurogenic inflammation. Structure activity studies with capsaicin-like molecules have suggested that a "receptor" should mediate the effects of capsaicin on sensory neurons. The cloning of the vanilloid receptor-1 (VR1) has confirmed this hypothesis. VR1 (TRPV1) belongs to the transient receptor potential (TRP) family of channels, and its activation by various xenobiotics, noxious temperature, extracellular low pH and high concentration of certain lipid derivatives results in cation influx and sensory nerve terminal excitation. TRPV1 may dimerise or form tetramers or heteromers with PLC-gamma and TrkA or even with other TRPs. TRPV1 is markedly upregulated and/or "sensitised" under inflammatory conditions via protein kinase C-epsilon-, cAMP-dependent PK- and PLC-gamma-dependent pathways or by exposure to dietary agents as ethanol. TRPV1 is expressed on sensory neurons distributed in all the regions of the gastrointestinal tract in myenteric ganglia, muscle layer and mucosa. There is evidence of TRPV1 expression also in epithelial cells of the gastrointestinal tract. High expression of TRPV1 has been detected in several inflammatory diseases of the colon and ileum, whereas neuropeptides released upon sensory nerve stimulation triggered by TRPV1 activation seem to play a role in intestinal motility disorders. TRPV1 antagonists, which will soon be available for clinical testing, may undergo scrutiny for the treatment of inflammatory diseases of the gut.