Leukodystrophies are inherited neurological disorders involving central nervous system white matter. They are uncommon in animals but a few, breed-specific entities have been described. In 2002, two young-adult, purebred Bullmastiff dogs from central New York State presented to their referring veterinarians displaying moderate to severe ataxia of all limbs, spastic tetraparesis that was worse in the pelvic limbs, and a diffuse, action-related, whole-body tremor. Clinical signs were insidious in onset and slowly progressive. Anatomic diagnoses considered were a C1-C5 lesion or, based on the whole-body tremor, a diffuse central nervous system disorder. No gross lesions were apparent in the brain or spinal cord. Histopathologically, numerous, multifocal, sharply demarcated, small, ovoid to angular areas of myelin pallor (plaques) were present throughout the major white matter tracts of the brainstem and spinal cord. These plaques, which often were traversed by axons, did not stain with luxol fast blue for myelin and were associated with minimal astrocytosis. Ultrastructural findings include occasional hypertrophic glia in white matter, rare unmyelinated segments of axons, and focal proliferation of tubule-containing cytoplasmic glial cell processes (oligodendroglial). The described clinical and morphological findings and age of onset are similar to the well-characterized, presumably hereditary, bovine syndrome known as Charolais ataxia or oligodendroglial dysplasia. This article presents the first description of a leukodystrophy in the Bullmastiff breed and the first report of oligodendroglial dysplasia in animals other than Charolais cattle.