Xenon and other inhalational agents induce cell and organ effects through different and only partially elucidated molecular mechanisms. In this study, we explored the gene transcription consequences of xenon exposure compared with nitrogen or nitrous oxide exposure in rat brain. Seven-day-old Sprague Dawley rats (n=24, 8 for each group) were exposed for 120 minutes to 75% xenon and 25% oxygen, 75% nitrogen and 25% oxygen (air), or 75% nitrous oxide and 25% oxygen. Using suppression subtractive hybridization, relative real-time polymerase chain reaction, and northern blot analyses of on/off gene expression, we were able to identify a set of genes that are significantly up-regulated by xenon exposure. These genes may help explain some of the molecular mechanisms that account for the neuropreconditioning effects exerted by xenon relative to nitrous oxide and air.