Extensive serological testing and HCV RNA determination by RT-PCR was performed in serum, PBMCs, and liver tissue in thirteen anti-HCV reactive patients with persistently normal liver tests. Absolute concordance in the status of HCV RNA between serum, PBMCs, and liver was noted. Five patients were HCV RNA positive but only three had mild histological changes. Eight patients were HCV RNA negative in all three sites and had virtually normal liver histology. Patterns of reactivity in RIBA 2.0 strip immunoblot assay did not differentiate viremic from nonviremic patients. ELISA testing using multiple individual HCV recombinant antigens from the structural and non-structural regions of HCV demonstrated mean antibody titers to the structural antigens, in particular HCV E2 antibodies, to be significantly lower in HCV RNA negative patients. The status of HCV RNA in the serum appears to infer the status of HCV RNA in the liver and PBMCs in patients with persistently normal liver tests. Patients with persistently normal liver tests and undetectable HCV RNA have probably spontaneously cleared HCV infection.