The clinical significance of hepatitis C antibodies (anti-HCV) in a healthy population was studied by liver function tests and liver biopsies. The patient population consisted of 195 (96.1%) of the 203 blood donors found to be either anti-HCV positive or indeterminate by a recombinant immunoblot assay (RIBA) during the first year of anti-HCV screening of 307,606 donors in Finland using a first generation enzyme-linked immunosorbent assay. Alanine aminotransferase (ALT) levels in 67 donors reacting positively and in 128 reacting indeterminately by a second generation RIBA (RIBA-4) were monitored to evaluate the prevalence of liver damage. Serum N-terminal type III procollagen (PIIINP) concentrations were measured in all donors who fulfilled our criterion for possible hepatitis C (ALT values over two times the normal upper limit on two occasions or over five times the normal upper limit on one occasion) and in 23 randomly selected RIBA-4 positive donors without ALT abnormalities (control group). Two (1.6%) of the RIBA-4 indeterminate donors had ALT values compatible with possible hepatitis C (negative by polymerase chain reaction) whereas there were 25 (37.3%) such individuals among the RIBA-4 positive donors (P < 0.0005). Twenty (80%) of the latter 25 RIBA-4 positive donors with possible hepatitis C consented to liver biopsy. Of these 20 donors, 11 (55.0%) were found to have chronic persistent hepatitis, four (20.0%) mild, three (15.0%) moderate, and two (10.0%) severe chronic active hepatitis.(ABSTRACT TRUNCATED AT 250 WORDS)