There is controversy about clinical management of patients who persistently have antibodies to hepatitis C virus (anti-HCV) but who have no symptoms and signs of liver disease. We have taken liver biopsy samples from 23 such patients (16 of whom had normal alanine aminotransferase [ALT] values) to assess prevalence of liver disease and to see whether anti-HCV and HCV-RNA correlated with histological findings. 16 patients had histological evidence of chronic hepatitis, which was not predicted by serum ALT or by the pattern of specificity of anti-HCV. All 16 cases with hepatitis C viraemia (HCV-RNA detected by polymerase chain reaction), including 9 with normal ALT, had chronic hepatitis on biopsy (p less than 0.001), whereas 7 HCV-RNA-negative cases had normal liver histology. These findings indicate that serum HCV-RNA is a sensitive and specific marker of liver disease in anti-HCV-positive subjects, independent of ALT values, and challenge the idea of the existence of "true" healthy carriers of HCV.