The cellular responses to ionizing radiation and other genotoxic stresses are complex and are regulated by a number of overlapping pathways. One such stress-signalling pathway is exemplified by the transcription factor p53, which can regulate the expression of a myriad of downstream genes in response to various stresses. We have recently demonstrated the utility of cDNA microarray hybridization to measure radiation stress-gene responses in p53 wild-type human cells. Our initial experiments also resulted in the identification of a number of new radiation-responsive genes. We have since extended these studies to a broader range of doses and timepoints, and identified a large set of genes regulated in response to ionizing radiation, as well as other stresses. These and other newly identified stress-responsive genes are being assembled in a stress-specific array, tailored for use in future genotoxic stress experiments. By focusing our efforts on a subset of responsive genes, we hope to rapidly obtain large stress-specific databases suitable for an informatics approach to analysis. Similar analytical approaches in our laboratory have previously yielded important mechanistic insights into the function of the gene GADD45, forming an important precedent for the utility of informatics analysis. The wide variation in responses observed for some stress-responsive genes in different cell lines, or in response to different genotoxic stresses, highlights the importance of cellular context to stress response, as well as the need for informatics approaches to the study of stress-specific gene response pathways.