The frequency of hepatitis A virus (HAV) contamination in mussels sold in south of Italy, where a high incidence of HAV infection both in resident people and in travelers is reported every year, was investigated during a three-year period. Mussels, collected from the markets of five big cities, were analysed by RT-nested-PCR to detect RNA-HAV and by an integrated method, cell culture-RT-PCR, to confirm the presence of infectious virus. On a total of 180 samples, 15.6% resulted contaminated by infectious HAV. The high percentage of mussels, potentially dangerous for consumers, and the diffuse habit to consume them raw or slightly cooked, can contribute to maintain the endemic status of HAV infection in some areas of the south of Italy.