Host cell gene expression during the course of a human adenovirus infection in synchronized primary human lung fibroblasts was analyzed using cDNA microarrays. The slow progression of the infectious cycle in these cells allowed a detailed examination of cellular gene regulation. In total, 988 unique genes were identified as differentially expressed more than 2-fold. The cellular gene expression profiles closely correlated to the progression of the infection. Based on the observed expression patterns, the deregulation of cellular genes' expression could be separated into four periods: (i) the immediate response of the host to incoming virus; (ii) deregulation of cellular genes involved in cell cycle, growth control, and antiviral response; (iii) steady-state regulation of cellular gene expression during viral DNA replication; (iv) targeting of cellular genes involved in intra- and extra-cellular structure at the late phase of infection. The struggle of the virus to gain control of TGF-beta and Wnt signaling, as well as the apoptotic pathways, was conspicuous.