Eastern equine encephalitis (EEE) was diagnosed (postmortem) in a sheep with clinical signs attributable to a central nervous system disease. The sheep was febrile and initially had front limb incoordination, which progressed to paralysis of both front and hind limbs during a course of 2 days. The sheep maintained an alert attitude with the ability to eat up to the time of euthanasia. The only clinical pathologic abnormalities were neutrophilia and lymphopenia without appreciable leukocytosis, a moderate hyperglycemia, and an elevated creatine kinase. Treatment included hydrotherapy for lowering body temperature, intravenous fluids, thiamine hydrochloride, tetanus antitoxin, antibiotics, and corticosteroids. The only gross lesion at the time of necropsy was a wet glistening surface of the brain (leptomeninges). Microscopically, there was severe nonsuppurative meningoencephalitis, poliomyelitis, and polyradiculoneuritis with mild multifocal neutrophilic infiltration. The EEE virus was isolated from the brain, and subsequent fluorescent antibody testing for EEE was positive on cell culture.