Microarray analysis of host cell gene expression during an adenovirus type 2 infection showed that the number of regulated genes, as well as the magnitude of change, was increased as the infection proceeded into the late phase. In contrast to the early phase of infection when the majority of differentially expressed genes were upregulated, expression of most of the regulated genes (82 out of 112) declined during the late phase. In particular, numerous TGF-beta inducible genes and several TGF-beta-independent growth-arrest-inducing genes were targeted. Of the 30 genes upregulated more than 2-fold at 20 h post-infection, nearly two-thirds of encoded proteins are involved in cell metabolism. The data indicate that adenovirus primarily targets cellular genes involved in antiviral defense, cell growth arrest and apoptosis, as well as cell metabolism, to ensure sufficient production of viral progeny.