Transcription-coupled repair of endogenous DNA damage appears crucial for the maintenance of the central and peripheral nervous systems. Ercc1 is essential for nucleotide excision repair and is also involved in recombination repair and the repair of interstrand cross-links. We have investigated the neurological phenotype of Ercc1-deficient mice where the liver dysfunction has been corrected by an Ercc1 transgene controlled by a liver-specific promoter. We observed poor coordination, ataxia and loss of visual acuity, but saw no evidence of the anticipated histopathological neurodegeneration, or of abnormal neuromuscular junctions. Instead we observed uraemic encephalopathy, a brain disease resulting from kidney failure. This diagnosis was supported by histopathological signs of kidney disease, as well as proteinuria. When we examined archival sections from neural-specific Ercc1 knockout mice, which showed the same reduced growth and died at the same age as the liver-corrected Ercc1 knockouts, we found no evidence of kidney pathology or encephalopathy. Thus, while some aspects of the Ercc1-deficient phenotype are indicative of functional neurodegeneration, we obtained no structural evidence for this. The structural changes observed in the brains of liver-corrected Ercc1 knockouts appear to be a secondary consequence of kidney failure arising from Ercc1 deficiency.