To evaluate the molecular and cellular bases of effects of ethanol on the brain, we utilized a differential display-polymerase chain reaction. Several cDNA fragments were differentially expressed in the hippocampus of control vs. ethanol-treated rats. One of these genes was homologous to the rat mitochondrial cytochrome c oxidase mRNA. Northern blot analysis revealed that the expression of this message in the whole hippocampus was clearly lower after ethanol treatment. Using in situ hybridization, we also found that cytochrome c oxidase mRNA expression, especially in the CA1 and CA3 of the hippocampal regions, was significantly decreased by ethanol treatment. As cytochrome c oxidase is related to oxidative stress, the present study suggests that ethanol might affect the brain through modulation of an oxidative stress reaction.