CNS histopathology of 2 cases of Vilyui encephalomyelitis (with neurological symptomatology of 7-month and 3-year duration) is presented. The picture demonstrates severe focal degenerative changes of neurons combined with nonpurulent inflammatory reaction in the pia mater and around the blood vessels of the cerebral and spinal cord white and gray matter. Characteristic features of the disease include swelling of the neurons and their processes, asymmetric thickening of the nuclear membrane, ectopy of the nucleoli and their exit from the nucleus and from the cell, karyocytolysis; formation of spongious foci and fine gliofibrous scars; considerable atrophic, edematous, and dystrophic changes in conduction tracts of the hemispheres, brain stem and spinal cord. An important pathohistologic feature of the disease is an extremely weak reaction of oligodendroglia which belongs to constitutional features of the CNS organization in patients with Vilyui encephalomyelitis and with which the progressive course of this severe disease is, probably, connected.