Interleukin-2 (IL-2) influences T cell proliferation and differentiation through regulation of a number of genes. Many such genes are known, yet their expression profiles have remained elusive. Using Affymetrix mouse genome arrays and the mouse T cell line CTLL-2, we studied the transcriptional response to IL-2 stimulation. A total of 2813 genes (represented by 3838 probes) showed > or =2-fold changes in expression level at one or more time points (10 were analyzed) during the first 24 h poststimulation. Cluster analyses indicated that these 2813 genes showed nine different expression patterns. Of these genes, approximately 1400 were not previously known to be regulated by interleukin-2 (IL-2). In the control, 666 genes with > or =2-fold changes at the mRNA level were identified in cells without IL-2 stimulation; 222 of them were among the 2813 IL-2-responsive genes. Possibly, the expression of these genes was altered because of changes in cell density or cell growth rate. The newly identified IL-2-responsive genes play roles in a variety of biologic processes, including signal transduction, apoptosis, cell cycle regulation, and transcription. Our data will be useful for studying biochemical events in IL-2 signaling.