When NCI-H292 human bronchial epithelial cells were infected with influenza A/Udorn/72(H3N2) virus, 152 host genes were identified as virus-stimulated genes (VSGs). The expression of these genes was increased more than 4-fold by the virus infection and reached to the level of more than one copy per cell. Seventy-three VSGs were also stimulated by interferon-beta (IFN-beta) treatment and they contained the genes known to possess antiviral activity. As a likely consequence, the production of progeny viruses was transient in H292 cells and the cells survived through infection. The stimulation of the VSGs is not mediated by IFNs but triggered by the infection itself at least at the early phase of infection. In A549 human lung epithelial cells, the increase of the VSG expression was less than 1/6 on the average of that in H292 and virus production continued until cell death. These indicate that some VSGs might constitute intracellular antiviral mechanisms. On the other hand, the NS1 protein of influenza virus shuts off host gene expression by inhibiting the polyadenylation-site cleavage of host pre-mRNAs. Therefore, balance of the shut-off and the activation of cellular genes during virus infection may be crucial in determining the outcome of infection.