ABSTRACT— A syndrome resembling human Primary Biliary Cirrhosis (PBC) and occurring spontaneously in a strain of domesticated rabbits from the Faenza region in Italy, is reported. The syndrome is characterized by histological liver changes consisting of chronic non-suppurative destructive cholangitis and copper accumulation, biochemical and immunological abnormalities mainly represented by an elevation of serum alkaline phosphatase and a positive antimitochondrial antibody test. The abnormalities were not observed in newborn rabbits from the same area nor in control rabbits from the island of Sardinia. A toxic effect related to some environmental factor may be responsible for the disease. Alternatively, a continuous process of partial inbreeding among consanguineous animals may have resulted in a selection of a strain genetically predisposed to the development of PBC. Whatever the etiology, the domesticated Faenza rabbit proves to be an interesting animal model for a chronic non-suppurative destructive cholangitis, very similar to the human disease known as PBC.