The infectivity of human herpesvirus 6 (HHV-6) in a human hepatoma cell line, Hep G2 cells, and the effect of HHV-6 on production of inflammatory cytokines in these cells were examined to analyze pathogenesis of HHV-6 in the liver. We demonstrated that Hep G2 cells were susceptible to infection with HHV-6, and produced infectious virus. Moreover, infection of Hep G2 cells by HHV-6 induced the expression of IL-8 mRNA, but not IL-1 beta. The effect on induction of IL-8 gene expression was observed only in Hep G2 cells infected with infectious virus, whereas both heat-inactivated HHV-6 and UV-irradiated HHV-6 did not change the IL-8 mRNA level in these cells. These data suggest that HHV-6 may induce the cytokine-mediated inflammatory response by infecting liver cells, which could result in liver dysfunction in vivo.