To determine the long-term course of non-A, non-B post-transfusion hepatitis. Follow-up in 1989 to 1992 of patients prospectively identified as having contracted non-A, non-B post-transfusion hepatitis between 1972 and 1980. A university hospital. Patients who were prospectively followed from receipt of blood products and in whom otherwise unexplained abnormalities in their serum alanine aminotransferase levels developed without serologic evidence of exposure to hepatitis A or B. The presence or absence of clinical evidence of liver failure or symptoms of chronic hepatitis. Of 90 patients identified in the 1970s, 80 were recontacted and evaluated between 1989 and 1992. Based on the current status of these 80 patients and on the last known status of the remaining patients, the following observations were made: 1) Although about 40% had some symptoms during the early phase of the disease, none subsequently experienced significant clinical problems related to hepatic inflammation; 2) eight patients (seven with chronic hepatitis) developed hepatic failure; and 3) life-table analysis showed that the probabilities of developing clinical evidence of cirrhosis after 16 years of disease in the entire cohort, in the subgroup who developed chronic hepatitis, in the patients who had hepatitis C, and in those with chronic hepatitis C were 18%, 21%, 17%, and 20%, respectively. For most of the study patients, non-A, non-B post-transfusion hepatitis was a biochemical and histologic disease that had not yet caused hepatic symptoms. If hepatic failure does occur, it is usually seen only after 10 or more years of disease. Before that time, many infected persons die due to other disease processes.