Abstract To determine whether the presence of hepatitis C virus (HCV) viremia correlates with the severity of liver disease in anti-HCV-positive apparently healthy blood donors, we studied 98 blood donors found positive for anti-HCV using enzyme-linked immunosorbent assay (ELISA). Each subject underwent a liver biopsy, a test for HCV RNA in the serum by polymerase chain reaction (PCR), and a panel of liver injury tests. As a result, 97% of the anti-HCV-positive blood donors had some type of histological abnormality: 22 (22%) had minimal changes, 1 (1%) had chronic lobular hepatitis, 40 (41%) had chronic persistent hepatitis (CPH), and 32 (33%) had chronic active hepatitis (CAH). Only 3 subjects had a normal liver histology. HCV RNA was detectable in the serum in 65% of the anti-HCV-positive donors. HCV RNA in serum was detectable in none of the donors with a normal liver histology, in 36% (confidence interval [ci], 17% to 59%) of those with minimal changes, in 70% (CI, 53% to 83%) of those with CPH, and in 87% (CI, 71% to 96%) of those with CAH ( P = .00001). HCV RNA was detectable in 75% of the donors with elevated (> 45 U/L) alanine transaminase (ALT) values and in 59% of those with normal ALT levels ( P = not significant). The incidence of chronic hepatitis was higher in HCV RNA-positive than in HCV RNA-negative donors (88% vs. 50%; P = .00005). By stepwise logistic regression, age older than 50 years (odds ratio = 17.5), an elevated ALT level (odds ratio = 74.4), and serum HCV RNA (odds ratio = 18.9) were independently associated with the presence of chronic hepatitis. In summary, in anti-HCV-positive blood donors the prevalence of HCV RNA in serum appears to correlate with the severity of liver injury and is greatest in CAH. The detection of serum HCV RNA in 36% of the donors with minimal changes on biopsy, all of them with normal ALT levels, suggests that a healthy HCV carrier state may exist.