Mitochondrial respiratory chain disorders are an established cause of liver failure in early childhood but they are probably under-diagnosed, partly due to under-recognition and partly due to the difficulty of investigation. It is particularly important to look for mitochondrial disorders if the liver disease presents with hypoglycaemia and lactic acidaemia or if it is accompanied by neurological, muscle or renal tubular abnormalities. Respiratory chain defects have been demonstrated in a number of patients who die of liver failure following severe epilepsy; this includes at least some cases of Alpers syndrome or 'progressive neuronal degeneration of childhood'. In mitochondrial liver disease, histology usually shows steatosis, often accompanied by fibrosis, cholestasis and loss of hepatocytes. Unless the clinical picture suggests a particular syndrome, such as Pearson syndrome, biochemical assays and histochemistry should be the initial investigations. Ideally, investigations should be carried out on liver as well as more standard tissues, such as muscle, since defects can be tissue-specific. Nuclear defects and mtDNA point mutations are probably responsible for many cases of mitochondrial liver disease but, as yet, the only identified molecular abnormalities are mtDNA rearrangements and mtDNA depletion. Treatment of mitochondrial liver disease is unsatisfactory. If the disease is confined to the liver, transplantation may be appropriate but in several patients transplantation has been followed by the appearance of disease in other organs, particularly the brain.