The relationship between plasma hepatitis C virus (HCV) RNA levels, antibody positivity, and hepatocellular damage were studied in 41 patients with non-A, non-B chronic liver disease. The patients were placed into two groups according to the plasma levels of HCV-RNA: plasma HCV-RNA level was estimated as high when detected by a one stage polymerase chain reaction (PCR) and as low when detectable only after a two stage PCR. Anti-HCV (first and second generation assays) and anti-GOR were also measured. The mean alanine aminotransferase (ALT) level of the high HCV-RNA group was 115 +/- 62 IU/l, whereas that of the low HCV-RNA group was 59 +/- 37 IU/l (P < 0.05). Patients with ALT levels above 100 IU/l had invariably a high level of HCV-RNA. There were no differences in clinical features in relation to the presence of anti-GOR or anti-HCV. Circulating HCV-RNA levels but not anti-HCV or anti-GOR antibodies correlated with hepatocellular damage.