This study was designed to evaluate serum HCV-RNA, liver histology, and RIBA-II pattern in asymptomatic anti-HCV positive subjects with persistently normal or slightly (i.e. < or = 1.5 times the upper limit of the normal range) elevated serum ALT levels. To this purpose, 22 asymptomatic anti-HCV positive subjects (11 men and 11 women, median age 40, range 21-70 years) underwent liver biopsy and determination of serum HCV-RNA. Positivity for anti-HCV was determined by ELISA-2 and by RIBA-II. Serum HCV-RNA was determined by PCR. Our data show that: 1) 9/22 symptom-free, anti-HCV positive subjects had histological features of chronic liver disease associated with ongoing HCV infection; 2) four subjects had no histological signs of chronic hepatitis and normal serum ALT levels despite positivity for serum HCV-RNA; 3) serum ALT levels did not discriminate HCV-RNA positive subjects with from those without chronic hepatitis; 4) in anti-HCV positive subjects with normal serum ALT levels, a positive RIBA-II pattern was not always predictive of HCV viraemia or chronic hepatitis while an indeterminate RIBA-II pattern was frequently associated with nonspecific liver changes or normal histology. In conclusion, based on these findings, "true" healthy carriers of HCV (i.e. subjects with normal serum ALT levels and no histological features of chronic hepatitis despite HCV viraemia) may exist.