HLA class I display on hepatitis B virus (HBV)-infected hepatocytes is important for limiting HBV infection. However, the effect of HBV replication on HLA class I expression on host cells has not been determined. Since acyclovir is known to inhibit HBV replication of the novel cell line HB611, which was transfected with HBV genome using human hepatoblastoma cells as the recipient and continuously replicates HBV DNA, we analyzed HLA class I expression on acyclovir-treated HB611 by quantitative flow cytometry. The results demonstrated that acyclovir treatment clearly increases the level of HLA class I on HB611, and suggested that HBV replication inhibits expression of HLA class I on infected hepatocytes. This effect of HBV replication on the host cell may be a means by which HBV evades immune surveillance to maintain chronic infection.