Five-hydroxytryptamine (5-HT, serotonin) is widely distributed within enteroendocrine (EC) and mast cells, and neurones of the intestines. In particular EC cells acts as epithelial sensory transducers and secrete 5-HT in response to mucosal stimuli. It is now clear that 5-HT plays an important role as an intestinal secretagogue in certain infectious and functional diarrhoeal states, in laxation, in nausea, and in intestinal hypersensitivity reactions. 5-HT stimulates active ion (and fluid) secretion. The secretory effects of 5-HT are mediated by epithelial 5-HT2 receptors and neuronal 5-HT1P, 5-HT3 or 5-HT4 receptors. The 3 neuronal 5-HT receptors are located on submucous processes of intrinsic (IPANs) and extrinsic (EPANs) primary afferent (sensory) neurones. The IPANs are activated via 5-HT1P and 5-HT4 receptors, which enhance the release of other neurotransmitters thereby strengthening pathways that are naturally activated, but do not initiate secretory reflexes per se. The EPANs are activated via 5-HT3 receptors and mediate signals to the CNS (vagal and spinal) and thus ameliorate cancer chemotherapy-associated nausea and the visceral hypersensitivity of diarrhoea-predominant irritable bowel syndrome (IBS). 5-HT activates both cholinergic and non-cholinergic pathways and the release of intracellular mediators (e.g. eicosanoids, calcium, phosphoinositols and cyclic nucleotides) in its secretory response. A transmembrane 5-HT transporter, the SERT, terminates epithelial serotonergic signalling. Epithelial SERT expression is decreased in conditions with inflammation (e.g. IBS and ulcerative colitis). Thus malfunction of the SERT may contribute to the pathogenesis of these conditions. Ultimately EC cells, SERT and 5-HT receptors might be pharmacological targets for treatment.