One hundred and thirty-five patients who developed non-A, non-B post-transfusion hepatitis mostly after cardiac surgery, were followed for a mean (+/- S.D.) of 90 +/- 41 months (range: 13-180) to evaluate clinical and histological outcome. Thirty-one cases resolved within 12 months, while 104 (77%) progressed to chronicity. Twenty-one of 65 (32%) biopsied patients developed cirrhosis at the end of the follow-up, and one further progressed to hepatocellular carcinoma. One patient had a complete histological remission (1%). The remaining cases had chronic active (37%), chronic persistent (27%) or chronic lobular hepatitis (3%). About half of the cases with cirrhosis developed portal hypertension, and three of these died due to esophageal varices hemorrhage, one due to liver failure, and one due to hepatocellular carcinoma. Out of 26 patients with the initial histologic diagnosis of chronic hepatitis that were rebiopsied during follow-up, 13 (50%) progressed to cirrhosis. These patients were significantly older than patients who did not develop cirrhosis (mean age 57 and 45 years respectively; p < 0.01). During acute hepatitis anti-HCV was positive in all but one of the 114 patients tested. Percentages were similar for patients who recovered (95%) and those who developed chronic hepatitis (100%). However, during follow-up, 71% of the 1st generation and 21% of the 2nd generation ELISA test patients with acute resolved hepatitis became anti-HCV negative, while the same figures in chronic cases were only 8.5% (p < 0.0001) and 1.4% (p = 0.012). This suggests a correlation between anti-HCV antibody activity, hepatitis C virus replication, and the development of chronic liver disease.