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Extracellular ATP is implicated in numerous sensory processes ranging from the response to pain to the regulation of motility in visceral organs. The ATP receptor P2X₃ is selectively expressed on small diameter sensory neurons^,,, supporting this hypothesis. Here we show that mice deficient in P2X₃ lose the rapidly desensitizing ATP-induced currents in dorsal root ganglion neurons. P2X₃ deficiency also causes a reduction in the sustained ATP-induced currents in nodose ganglion neurons. P2X₃-null mice have reduced pain-related behaviour in response to injection of ATP and formalin. Significantly, P2X₃-null mice exhibit a marked urinary bladder hyporeflexia, characterized by decreased voiding frequency and increased bladder capacity, but normal bladder pressures. Immunohistochemical studies localize P2X₃ to nerve fibres innervating the urinary bladder of wild-type mice, and show that loss of P2X₃ does …