Two patients are reported who presented with progressive impairment of neurological and intellectual function, and intractable fits. In both the disease ran a fluctuating course. There was evidence of mitochondrial dysfunction, serum levels of pyruvate and lactate being four to six times normal. Involvement of mitochondria in different organs was suggested by histochemical and ultrastructural investigations of muscle and heart tissue. The children died at nine years and twelve months, respectively. In both autopsy revealed cardiomyopathy and renal abnormalities. The brain showed severe lesions indistinguishable from subacute necrotizing encephalomyelopathy (SNE), the brunt of which was borne by the cortex.