Alterations in gene expression are thought to help mediate certain effects of alcohol in the brain. We have analyzed the expression of approximately 24,000 genes using oligonucleotide microarrays to examine the brain expression profiles in two strains of inbred mice, C57BL/6J and DBA/2J, following exposure to an acute dose of ethanol. Our screen identified 61 genes responding to the ethanol treatment beyond a 1.5-fold threshold, with 46 genes altered in both mouse strains and 15 altered in only one strain. Approximately 25% of the genes were selected for confirmation by reverse transcriptase polymerase chain reaction with an 87% success rate. The genes identified have roles in cell signaling, gene regulation, and homeostasis/stress response. Although some of the genes were previously known to be ethanol responsive, we have for the most part identified novel genes involved in the acute murine brain response to ethanol. Such genes have the potential to represent candidate genes in the search to elucidate the molecular pathways mediating ethanol's effects in the brain.