Cell-to-cell interactions and synaptic integration may occur within taste buds prior to signals being exported from these peripheral sensory organs to the CNS (Roper, 1992; Kaya et al., 2004). In principle, these interactions could include chemical and electrical synapses between taste cells and synapses from taste cells to sensory afferent fibers. Knowing which transmitters are released at synapses in taste buds would help clarify how signals are processed in taste buds but to date this information is lacking. A number of neurotransmitter candidates have been proposed for taste bud synapses, including serotonin (5 hydroxytryptamine, 5HT), glutamate, acetylcholine, ATP, peptides and others, but none has been unambiguously identified (reviewed by Nagai et al., 1996). On balance, the preponderance of evidence suggests that 5HT is one of the transmitters. For example, 5HT is found in a subset of taste cells in a wide variety of species (Kim and Roper, 1995). Taste bud cells that possess synapses with nerve fibers take up the 5HT precursor (Takeda, 1977; Yee et al., 2001), and tryptophan hydroxylase, the enzyme that converts tryptophan to 5 hydroxytryptophan (5HTP), is found in taste buds (Cao et al., 2004). There is indirect evidence from autoradiographic studies that amphibian taste cells release 5HT when they are depolarized (Nagai et al., 1998). Pharmacological and molecular biological studies suggest that taste cells express 5HT1A-like receptors and primary afferent fibers possess 5HT3 receptors (Delay et al., 1997; Herness and Chen, 1997; Kaya et al., 2004). Yet despite all the above evidence, one of the canonical criteria for identifying synaptic neurotransmitters, namely detecting its release from stimulated synapses, has yet to be established for 5HT in taste buds. We have addressed this question by using biosensor cells that are sensitive to 5HT to reveal transmitter release from mouse taste buds during sensory stimulation. The results indicate that depolarizing mouse taste cells with KCl or stimulating them with sweet and bitter tastants elicits 5HT release. Collectively, these data firmly identify 5HT as a taste cell neurotransmitter.