A seroepidemiological study was carried out in 15 primary health care (PHC) centres in rural Greece to determine the prevalence of hepatitis C virus (HCV) in the surgeries of Greek General Practitioners (GPs) and to further clarify the transmission of hepatitis C in Greece. Serum samples were obtained from 1961 subjects (1259 females) aged ≥ 15 years, who visited GP surgeries between July 1996 and February 1997 in 15 PHC centres located in three large Greek regions (Macedonia, Attika and Crete). Subjects who participated in the study fulfilled the following criteria: history of blood transfusion; hospital admission of > 7 days’ duration without surgical or other intervention; use of intravenous drugs (current or previous); or women with a history of medical or paramedical abortion. Nearly 65% (1263 subjects) of the participants in this study reported hospital admission with a length of stay > 7 days. Antibodies to HCV (anti-HCV) were found in 67 participants (3.5%), 41 of whom were females and 44 of whom were aged ≥ 61 years. The highest prevalence (4.8%) of anti-HCV was found in Crete, and differences among the Greek regions were statistically significant (P < 0.05). Multivariate statistical analysis showed that in addition to regional differences, the following variables had a statistically significant effect on the prevalence of anti-HCV: history of dental surgery; use of intravenous drugs; hospital admission for > 7 days; and the high consumption of alcoholic drinks. Hence there is a significant variability in the prevalence of hepatitis C in well-defined PHC areas of Greece. Several risk factors for acquiring HCV infection have been identified. Screening for HCV risk factors may enable Greek GPs to identify HCV-infected patients.