The regulation of mitochondrial energy metabolism is not only important for normal functioning of neurones, but also appears to be essential during acute damage and neurodegeneration in the central nervous system. This makes mitochondria an interesting regulatory target for therapeutic approaches. Oestrogen is well-recognised as a protective hormone in the central nervous system under pathological threats. In the present study, we analysed the influence of oestrogen on the expression of mitochondria-encoded genes and mitochondrial activity in spinal cord cells both in vitro and vivo. Hormone application increased the transcription of mitochondrial respiratory chain enzymes (MRCE). This effect was observed in cultured spinal cord neurones, where it was inhibited by a nuclear oestrogen receptor (ER) antagonist and mainly mediated by the activation of ERbeta. No effect of oestrogen was observed in cultured spinal cord astroglia. In addition, the mitochondrial transcription factor A and nuclear respiratory factor 1 were up-regulated by oestrogen in a similar way as MRCE in vitro, and ATP levels were elevated after the application of the specific ERbeta agonist 2,3-bis(4-hydroxyphenyl)-propionitrile in cultured spinal cord nerve cells. The exposure of young male mice to oestrogen yielded increased levels of MRCE transcripts in the spinal cord. These data clearly show that systemic application of oestrogen stimulates MRCE expression in the spinal cord and predominantly in neurones. Further studies are required to demonstrate the potency of oestrogen to counteract pathological damage by stabilising mitochondrial performance.