There is controversy about clinical management of individuals who persistently have hepatitis C virus antibodies (HCVAb) but who have no symptoms or signs of liver disease. Liver biopsy samples were taken from 15 individuals, all of whom had normal alanine aminotransferase (ALT) levels, to determine the prevalence of liver disease and whether HCVAb and HCV-RNA correlate with histological findings. Eleven patients with hepatitis C viremia had histological evidence of chronic hepatitis on biopsy. On the other hand, four HCV-RNA-negative individuals had almost normal liver histology. These findings indicate that serum HCV-RNA is a sensitive and specific marker of liver disease in HCVAb-positive subjects, independent of ALT levels. Furthermore, these results suggest that there are very few histologically healthy carriers of HCV among HCV-RNA-positive individuals.