Acoustic overstimulation has very different outcomes in birds and mammals. When noise exposure kills hair cells in birds, these cells can regenerate and hearing will recover. In mammals, however, the hair cell loss, and resulting hearing loss, is permanent. Changes in gene expression form the basis for important biological processes, including repair, regeneration, and plasticity. We are therefore using a battery of molecular approaches to identify and compare changes in gene expression following noise trauma in birds and mammals. Both differential display and subtractive hybridisation were used to identify genes whose expression increased in the chick basilar papilla immediately following exposure to an octave band noise (118 dB, centre frequency 1.5 kHz) for 4-6 hr. Among those upregulated genes were two involved in actin signalling: the CDC42 gene encoding a Rho GTPase, and WDR1, which encodes a protein involved in actin dynamics. A third gene, UBE3B, encodes an E3 ubiquitin ligase involved in protein turnover. A fourth gene encodes a cystein-rich secreted protein that may interact with calcium channels. To examine the mammalian response, gene microarrays on nylon membranes (Clontech Atlas Gene Arrays) were used to examine global changes in gene expression 30 minutes after TTS (110 dB broadband noise 50% duty cycle) or PTS (125 dB, 100% duty cycle) noise overstimulation (each for 90 minutes) in the rat cochlea. Several genes, including classic immediate early response genes such as c-fos, EGR1/NGFI-A, and NGFI-B, were upregulated at this early time point following the PTS exposure, but were not upregulated following the TTS exposure.