Arboviral encephalitis in domestic animals in the United States is rare with the exception of equine encephalomyelitis in horses. This report describes 2 cases in which La Crosse virus (LACV) was isolated from canine littermates with acute clinical encephalitis or sudden death. Both cases occurred in the southern region of the state of Georgia and were submitted as cadavers for necropsy to the Veterinary Diagnostic and Investigational Laboratory (VDIL) in Tifton, Georgia. On May 9, 1988, 4 2-week-old mixed-breed littermate puppies exhibited acute signs of central nervous system disease and were taken to a veterinarian. Three of the puppies had repeated seizures during the clinical examination. Because the clinical signs were compatible with a diagnosis of canine distemper virus encephalitis, the veterinarian issued a poor prognosis; the 3 puppies were euthanized and submitted to the VDIL for necropsy. The fourth puppy was mildly affected and was sent home without follow-up. On May 28, 1991, illness and deaths occurred in a litter of 7 8-day-old Brittany spaniel puppies. Two puppies were found dead and were taken to a veterinarian, who submitted the cadavers to the VDIL for necropsy. A third puppy was moribund and experienced breathing difficulty and died within the following hour. The veterinarian examined the 4 remaining puppies later that day and found them to be healthy. The same veterinarian had examined the entire litter 5 days previously. At that time, the animals appeared healthy, and tail docking was performed. A necropsy was performed on each of the 3 mixed-breed and 2 Brittany spaniel puppies submitted to the VDIL. Macroscopically, the brain of each puppy was severely and diffusely malacic. Other tissues appeared normal. Representative sections of lung, heart, liver, kidney, urinary bladder