The majority of patients with hepatic cirrhosis in Japan do not have a history of acute hepatitis or alcoholism. Twenty-nine patients with hepatic cirrhosis which were thought as random samples from cirrhotic patients without a history of acute hepatitis or alcoholism were Human Leukocyte Antigen (HLA) typed. Association of HLA-B5 and -BW22-J with hepatic cirrhosis of apparently unknown etiology was found in p less than 0.003, and p less than 0.01, respectively (128 controls). A predisposition linked to HLA-B5 or -BW22-J related gene or genes seems to play a role in the development of hepatic cirrhosis, at least in a substantial part of patients with hepatic cirrhosis of apparently unknown etiology in Japan.