The phenotypes of alpha-1-antitrypsin have been analyzed by isoelectric focusing on polyacrylamide gels in 232 healthy Japanese blood donors and in 240 Japanese patients with chronic liver diseases: 69 with chronic active hepatitis, 122 with liver cirrhosis, 41 with hepatocellular carcinoma and 8 with primary biliary cirrhosis. The liver cirrhosis patients had a gene frequency of 0.07 for P1*M3, which was significantly higher (P less than 0.01) than that (0.03) in blood donors. The gene frequency of P1*M3 was significantly increased in cryptogenic liver cirrhosis (P less than 0.05), and there was a tendency toward an increased frequency of P1*M3 in post-transfusion groups, and in primary biliary cirrhosis. There were also tendencies toward increased frequencies of P1*M3 in cryptogenic and post-transfusion groups of patients with chronic active hepatitis. The present study indicates that P1*M3 is a genetic or predisposing factor for chronic liver diseases, especially for cryptogenic and/or non A-non B viral chronic liver disease and also for primary biliary cirrhosis.