Betsy, a 4.5 year-old female spayed Cavalier King Charles Spaniel, was presented to the Cornell University Hospital for Animals for evaluation of acute blindness, inappetance, and lethargy. Ophthalmic examination revealed keratoconjunctivitis sicca in both eyes (OU), absent menace OU, decreased pupillary light responses OU, posterior vitreal haze OU, and optic disk enlargement OU. A diagnosis of optic neuropathy was pursued because of bilaterally enlarged optic disks in the absence of other localizing clinical signs or ophthalmic abnormalities sufficient to cause blindness. The presumptive diagnosis of optic neuritis due to granulomatous meningoencephalomyelitis (GME) was based upon: peripapillary retinal vasculitis on fluorescein angiography, severe lymphocytic inflammation within the cerebrospinal fluid (CSF), negative infectious disease serum and CSF titers, and favorable response to immunosuppression. Granulomatous meningoencephalomyelitis is an inflammatory disease of the central nervous system (CNS) of undetermined etiology and poor prognosis. Successful treated of this dog's GME consisted of conventional treatment using oral prednisone and non-conventional treatment using an additional immunosuppressive agent, cytosine arabinoside.