A case is reported in which non-A, non-B posttransfusion hepatitis was followed serially by chronic persistent hepatitis, chronic active hepatitis, and liver cirrhosis that finally developed into hepatocellular carcinoma. The patient died after a 19-year clinical course. During the last 8 years, repeated attempts to identify serum hepatitis B surface antigen, antibody to hepatitis B surface antigen, and antibody to hepatitis B core antigen were consistently negative. Liver biopsy was performed five times during the clinical course, and at autopsy, liver tissue was obtained from four different nontumor regions. These specimens were investigated by a peroxidase immunoenzyme method which failed to detect hepatitis B surface antigen and hepatitis B core antigen. Non-A, non-B posttransfusion hepatitis may become chronic and sometimes may advance to hepatocellular carcinoma.