To clarify the long-term clinical significance, antibody to hepatitis C virus (HCV) was examined using core (p22) and nonstructural (C100-3) protein assays in sera of 18 patients with non-A,non-B posttransfusion hepatitis (PTH-NANB) who were selected retrospectively. Each patient had been followed for more than 5 years after the development of the disease. They were divided into three groups according to clinical outcome: acute hepatitis that resolved within 1 year, group 1 (n = 3); chronic hepatitis that resolved within 1-4 years, group 2 (n = 4); and chronic hepatitis that persisted for 5 years or longer, group 3 (n = 11). Sixteen of the 18 were positive for anti-C100-3 and anti-p22, one was positive for anti-p22 alone, and one was negative for both. In ten of the 16 (62.5%), anti-p22 appeared before anti-C100-3. The anti-C100-3 titer peaked about 12 months after disease onset in all cases and thereafter declined gradually, finally becoming negative in groups 1 and 2, while the titer fluctuated in group 3. The mean titer in group 3 at 12 months (69.2 units) significantly exceeded that of groups 1 (4 units) and 2 (8.2 units). Group 1 was seronegative for HCV antibodies and HCV RNA at the last examination, suggesting the cessation of HCV replication. Group 3 remained positive for those markers, indicating the continued replication of HCV.(ABSTRACT TRUNCATED AT 250 WORDS)