The nervous system in patients with cerebro-hepato-renal syndrome appeared to be affected at various tissue levels. There was evidence of a migrational disorder manifested by polymicrogyria and lack of normal neuronal maturation. There was dysmyelination of the white matter associated with accumulation of neutral fat in astrocytes. Within the peripheral nerves, masses of tangled neurofilaments producing dystrophic axons were demonstrated by electron microscopy. These findings could be explained on the basis of a genetic metabolic defect, one that involved particularly the amino acids. The defect may have interfered with the normal intercellular reaction during embryogenesis resulting in the malformation of multiple organs. The same metabolic abnormality could have caused the hepatic damage and disturbance in normal myelination during the neonatal period.