Experiments were designed to compare the transcriptional response to ionizing radiation (IR) of wild-type (WT) and ataxia telangiectasia (AT) cells. mRNA levels were assessed 2, 4 and 24 h after exposure to equitoxic doses using cDNA microarrays. Data reveal distinct patterns of gene expression between AT and WT cells since IR-responsive genes were mostly cell-type specific, this group representing 87 and 94% of the responding genes in WT and AT cells, respectively. In both cell lines, transcriptional alterations of genes associated with proliferation correlated with the observed cell cycle and growth data. Deregulated genes involved in apoptosis suggest that wild-type cells were more prone to cell death by apoptosis than AT cells. Furthermore, genes associated with the response to oxidative stress were particularly deregulated in wild-type cells whereas alterations of genes related to unexpected pathways including RNA processing, protein synthesis and lipid metabolism were specifically found in irradiated AT cells. These data suggest that under radiation conditions leading to a similar survival of WT and AT cells, the mechanisms triggered after radiation were mainly dependent on ATM status and thus on the intrinsic radiosensitivity.