A young male Bernese mountain dog presented with neurologic abnormalities consisting of nonambulatory tetraparesis, generalized tremors, and depressed mental status. At necropsy only a mild enlargement of the lateral ventricles was seen. The histologic examination revealed the presence of eosinophilic deposits consistent with Rosenthal fibers (RFs) throughout the white matter of the central nervous system. There was also a marked proliferation of abnormally large astrocytes and limited myelin changes. RFs were most prominent in perivascular, subpial, and subependymal areas, where they were perpendicularly located, producing a pallisaded arrangement. Immunohistochemically, RFs were strongly positive for glial fibrillary acidic protein (GFAP), and when they were examined ultrastructurally they appeared as electron-dense amorphous masses located within the processes of astrocytes, most particularly in the perivascular feet. The histologic and immunohistochemical findings of this canine case were consistent with the published neuropathologic descriptions of Alexander disease in humans and in a few dogs, a rare condition that in humans has been shown to be caused by dominant mutations in the GFAP gene.