Chronic hepatitis (CH) is a common diagnosis in dogs, and can range clinically from mild liver enzyme elevations to overt liver failure. CH is over-represented in certain breeds of dogs, such as Doberman Pinschers, Cocker Spaniels, Skye Terriers, Dalmatians, and West Highland White Terriers, but can affect any breed of dog. CH is linked to a genetic defect of copper storage in Bedlington Terriers, but in all other dogs, the causes remain obscure. Approximately 20 percent of human patients with CH have autoimmune hepatitis, characterized by auto-antibodies to liver proteins. These auto-antibodies in humans assist in the diagnosis of CH, and are used to determine prognosis and to monitor therapy. We hypothesize that dogs with chronic hepatitis (CH) also develop auto-antibodies to specific canine liver proteins, and that these antibodies may be useful in determining the cause of CH in some dog breeds. In preliminary studies, we have found antibodies to liver microsomal proteins in several dogs with CH, which were absent in dogs without spontaneous liver inflammation. The purpose of this study is to characterize the prevalence of antibodies to different canine liver proteins in dogs with spontaneous CH, using immunoblotting, and to compare this to healthy dogs, dogs with non-inflammatory liver disease (vacuolar hepatopathy), and dogs with drug-induced (non-spontaneous) hepatic inflammation. In addition, we will determine the identity of common auto-antibody targets in dogs with CH, using mass spectrometry. The characterization of specific auto-antibodies in dogs with CH may contribute to the diagnostic classification of this disease syndrome in dogs. These findings may also allow the generation of testable hypotheses about the role of auto-antibodies in the pathogenesis of CH in certain breeds of dogs.