The prevalence of hepatitis C virus (HCV) infection in 182 prospectively followed adult patients (110 males, 72 females) with acute non-A, non-B hepatitis and its correlation with progression to chronic hepatitis were studied. These patients were followed for a mean of 24.7 +/- 13.1 (range, 6-57) months. By using a specific enzyme immunoassay for the detection of antibodies against C100-3 polypeptide of HCV, 96 (52.7%) were found antibody positive. HCV was implicated in 64/89 (71.9%) of the cases with classical parenteral exposure but only in 18/64 (28.1%) of the community-acquired cases. Progression to chronic hepatitis was observed more frequently in antibody-positive than in antibody-negative cases (60/96 or 62.5% vs. 27/86 or 31.4%, P = 0.00002). Progression was also observed more often in males than in females (66/112 or 58.9% vs. 21/70 or 30.0% P = 0.0001), both in the antibody positive (48/68 or 70.6% vs. 12/28 or 42.9%, P = 0.01) and in the antibody negative (18/44 or 40.9% vs. 9/42 or 21.4%, P = 0.043) cases. These data indicate that (a) acute hepatitis due to HCV is characterized by a high rate of chronicity, especially in males, and (b) a non-A, non-B, non-C agent or a different strain of HCV may be responsible for the majority of the community-acquired cases of non-A, non-B hepatitis in Greece.