The activity of antibodies to hepatitis C virus (anti-HCV) was investigated in 80 patients with chronic non-A, non-B liver diseases. Serum anti-HCV titer was determined by the "Ortho-HCV" enzyme-linked immunosorbent assay with some modifications to quantify the activity. Anti-HCV was positive in 82.5% of cases (66/80). Anti-HCV occurred significantly less often in the patients with chronic persistent hepatitis (8/13, 61.5%) than in those with chronic active hepatitis (42/49, 85.7%) (p less than 0.05). Anti-HCV titer of the patients with chronic persistent hepatitis and that with chronic active hepatitis was significantly higher than that with liver cirrhosis (p less than 0.01 and p less than 0.05). There was no correlation between anti-HCV titer and histology activity index in chronic hepatitis. Serial study demonstrated that anti-HCV titer decreased more frequently in the patients who responded to IFN alpha therapy (11/22, 50.0%) than in those who did not respond to IFN alpha therapy (0/10, 0%) (p less than 0.01). These results indicate that anti-HCV level does not correlate with the activity of hepatitis, but that it decreases in accordance with the disease progression to liver cirrhosis or with the response to IFN alpha therapy.