Granulomatous meningoencephalitis (GME) is a sporadic, rapidly progressive disease of unknown etiology. Clinical signs can be quite variable and prognosis is dependent upon the morphologic form of GME and severity of the underlying lesion. Definitive diagnosis necessitates histopathological examination of neuronal tissues and this is often impractical antemortem. Granulomatous meningoencephalitis is likely to be overdiagnosed in patients with encephalitis of unknown etiology. As such, we propose the terminology of meningoencephalitis of unknown etiology (MUE) when clinical signs are consistent with GME but CNS tissues are unavailable for histopathologic studies. Although immunosuppression has formed the cornerstone of MUE therapy, corticosteroids typically are ineffective as a sole therapy for long-term disease control. To date, the use of cytosine arabinoside as a therapeutic agent for the treatment of MUE has received little attention in the veterinary literature. Here, we report the use of a cytosine arabinoside-prednisone therapy protocol for the treatment of MUE in 7 dogs. The 7 patients were included based upon history, clinical signs, CT analysis, CSF analysis, and negative diagnostic investigations for infectious encephalitis. The treatment protocol consisted of administering cytosine arabinoside (Cytosar) at a dose of 50 mg/m2 SQ BID q3 weeks for a duration of 4 months, along with a tapering dose of prednisone. The mean survival time for the 7 dogs in this study was 291 days, with 6 of the 7 dogs alive. Six dogs were categorized as in clinical remission and 1 dog died after 101 days. In a retrospective study, dogs with focal GME that were treated with sole corticosteroid therapy had a mean survival time of 41 days (Munana and Luttgen 1998) suggesting that treatment with corticosteroids alone is unsatisfactory. While preliminary in nature, the case series presented in this report suggest a potentially important role for cytosine arabinoside in the treatment of dogs with MUE.