Cavernous sinus syndrome (CSS) is characterized by deficits in more than one of the cranial nerves (CN) that traverse the cavernous sinus at the base of the cranial vault: CN III (oculomotor), IV (trochlear), VI (abducens), and the first two branches of CN V (trigeminal). Records from 4 dogs and 8 cats with CSS diagnosed over a 14-year period were reviewed. The most common clinical signs were ophthalmoparesis or ophthalmoplegia, mydriasis with no direct or consensual pupillary light reflexes, ptosis, decreased corneal sensation, and decreased retractor oculi reflex. All cats had initial signs referable to a left CSS lesion (one had bilateral CSS), whereas in all dogs the lesions were localized to the right cavernous sinus. Median ages at diagnosis were 9 and 10 years of age for dogs and cats, respectively. Cerebel lomedullary cisternae cerebrospinal fluid analysis in 6 animals was useful as a sensitivebut nonspecific diagnostic test of an intracranial inflammatory or neoplastic lesion. Magnetic resonance imaging scans provided a more definitive diagnostic test in all dogs, revealing a contrast-enhancing mass on T1 weighted scans in the region of the cavernous sinus. A definitive pathological diagnosis was obtained in 2 dogs: a primary intracranial neoplasm and a metastatic intracranial neoplasm. A definitive diagnosis was obtained in 6 cats: metastatic neoplasm (n =1), primary intracranial neoplasm (n = I), primary intracranial infectious disease (n = 2). and associated systemic infectious disease (n = 2). The prognosis associated with CSS in dogs and cats was considered guarded to poor. J Vet Intern Med 1996;10:65–71. Copyright © 1996 by the American College of Veterinary Internal Medicine.