Regulation of P2X(2) receptor (P2X(2)R) expression in the rat cochlea in response to noise was analysed. Sustained loud sound (90-120 dB white noise, > 6 h), increased P2X(2)R mRNA and protein levels in rat organ of Corti and spiral ganglion (primary auditory neurones). P2X(2)R expression by the type I spiral ganglion neurones, which innervate the inner hair cells via the inner spiral plexus, was confirmed by confocal immunofluorescence. This also revealed increased P2X(2)R labelling of outer hair cell (OHC) stereocilia and cuticular plates, reflecting trafficking of greater numbers of ATP-gated ion channels assembled with P2X(2)R subunits to the transducer site. Whole-cell voltage clamp of OHC confirmed the noise-induced up-regulation of ATP-gated inward currents. These data indicate that regulation of P2X(2) receptor gene expression in the cochlea is adaptive, with sustained loud sound promoting increased transcription and translation specifically at sites regulating hearing sensitivity and auditory neurotrans-mission.