To determine whether or not mice are susceptible to hepatitis E virus (HEV) infection, C57BL/6 mice were experimentally infected with genotypes 1, 3 and 4 HEV by intravenous injection. Serum and stool samples were collected and used to detect HEV RNA and anti-HEV antibodies by RT-PCR and ELISA. The virus infection was monitored up to two months after inoculation; however, none of the serum or stool samples was positive for virus replication, demonstrating that C57BL/6 mice were not susceptible to HEV.