In an autopsied case of chronic multiple sclerosis, many axons in some demyelinated plaques of the spinal cord had remarkably increased diameters and reduced argentophilia. The increase in axonal diameter extended for some distance and was restricted to the demyelinated areas. A review of 22 autopsy cases of chronic multiple sclerosis revealed similar findings in the plaques of the spinal cord in seven cases. They were also noted in the brain but much less frequently. On electron microscopy, the neurofilaments in these enlarged demyelinated axons were not closely packed but were separated by an increased amount of electron-lucent axoplasm. It is thought that this finding may be a manifestation of increased water content in the axoplasm secondary to increased permeability of the demyelinated axolemma.