Mitochondrial accumulation has been reported at sites of degenerating nerve fibres. The reason for focal accumulation of mitochondria within axons has not previously been investigated. The aim of this study was to quantitate changes in mitochondrial concentration within demyelinated axons and determine if these changes were due to obstruction of the free passage of organelles within the fibre. The average number of mitochondria per unit area of axon within axons of normal cat optic nerve and optic nerve in which demyelination had been induced with anti-galactocerebroside (GC) was determined using transmission electron microscopy. Increased numbers of mitochondria were demonstrated at the site of demyelination, peaking at approximately two and a half times the value for normal non-lesioned nerves at 6-7 days after anti-GC administration [0.66+/-0.06 (SD) mitochondria per microm2 of axon compared to 0.28+/-0.04 in controls; P < 0.05]. The mitochondrial concentration gradually decreased over the next 20 days towards normal values. The concentration of mitochondria within non-myelinated axons of cat retina (0.55+/-0.18) was also determined and shown to be comparable to the values for the demyelinated optic axons (0.66+/-0.06). It is proposed that the accumulation of mitochondria within demyelinated axons reflects the adaptive process of the axon during the early restoration of impulse conduction rather than the obstruction of the free passage of organelles within the fibre.