Hepatitis E virus (HEV) infection has been considered to occur via faecal-oral transmission and is an important public health concern in developing countries, while such HEV transmission had been recognized to be extremely rare in industrialized countries including Japan. Recently, however, increasing cases of hepatitis E are reported in Japan and several cases are described as transfusion-transmission. Many reports from Japan suggest that eating undercooked meat and ⁄ or liver of pigs and other animals is associated with a high risk of acquiring HEV infection. According to the reports by Japanese investigators including ourselves, the HEV RNA-positive donors had no history of recent travel abroad in areas where HEV was hyperendemic [1]. Some isolates from the HEV RNA positive donor samples showed close sequence homology with the isolates from pigs in Japan, indicating that HEV transmission is probably associated with the consumption of undercooked or inadequately cooked pig meat [2]. Thus, HEV is regarded as a zoonotic agent in Japan.Characteristics of hepatitis E in Japan can be summarized as follows. More than 200 cases of hepatitis E have been recently reported [3]. The patients are dominantly middleor high-aged males. The isolated HEVs are genotype 3 and genotype 4 and regarded as indigenous strains in Japan. Genotype 4 viruses may cause more serious symptoms. In about 60% of the cases, their routes of infection remain unknown, although 31% of the cases are confirmed to be zoonotic food-borne. There are several reported cases of transfusion-transmission.So far, we have experienced four cases of transfusiontransmitted hepatitis E (TTHE). In 2004, we reported the first molecularly confirmed case of TTHE. However, infection route of the causative donor was not very clear. To assess the risk of the transfusion-transmission of HEV, we started a series of HEV surveys in blood donors of Hokkaido and nationwide Japan.For the surveys of HEV prevalence in blood donors, we tested samples of the donors who were disqualified due to high ALT level over 200 IU ⁄ l [4]. Samples of donors with ALT elevation during the 1-year period from April 2003 were collected from all-over Japan and tested for HEV markers: IgM anti-HEV, IgG anti-HEV and HEV RNA. As for donors with ALT elevation, Hokkaido was the highest region for all three HEV markers. Also, HEV prevalence was higher in eastern Japan than in western Japan. Among HEV markers of donors with ALT elevation, positive rate of IgG anti-HEV showed clear age-dependency, while there was no age-dependency in IgM anti-HEV or HEV RNA.In the next step, we tested the HEV prevalence of qualified donors. Age-and gender-matched samples of qualified donors were collected from all-over Japan. Again, higher prevalence of HEV IgG was observed in eastern Japan. The positive rates in female donors were lower than that in male donors. There is a clear age-dependency in IgG anti-HEV prevalence in qualified donors. As for IgM anti-HEV, positive samples were too few to draw any conclusion.Meanwhil...