Greece is a country of intermediate endemicity for hepatitis B and low endemecity for hepatitis C with a downward trend during the last years. In the present study we investigated the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection in the region of South-Western Greece and tried to identify the most important risk factors of transmission. This is a unique epidemiological study, as it is the first community based study in the general population of Greece, with a methodological approach based on multi-staged random sampling. The prevalence of HBV infection seems to be decreasing with a 22.6% rate of HBV markers and a 2.1% rate of chronic HBV carriers. We found male sex, old age and intrafamiliar exposure as the major independent risk factors of HBV transmission, while sexual contact, absence of condom prophylaxis and living in rural areas seem to have also a significant impact for HBV infection. No relation was found between HBV transmission and working in health care facilities, pre-existing hospital admissions and history of transfusion. The prevalence of anti-bodies to the HCV was found 0.5%, even lower than the rate reported in the Mediterranean region. Parenteral exposure was the main risk factor for the transmission of HCV infection.