Rapamycin, an immunosuppresant drug, prevents interleukin 2 (IL-2) induced proliferation of T-cells. Although the signalling pathway affected by rapamycin is poorly understood, current evidence indicates that the drug acts by inhibiting the translation of specific mRNAs. To identify mRNAs translationally regulated by IL-2 and/or rapamycin, we screened high density oligonucleotide arrays with probes prepared from polysomal mRNA from the IL-2 dependent human Kit-225 and mouse CTLL-2 cells. In Mouse 11k chips containing 11,000 genes (known genes and ESTs), 5% of genes showed significant polysome profile change after rapamycin treatment. The rapamycin sensitive genes include translation control molecules, such as ribosomal proteins and elongation factors, secreted proteins, cytoplasmic signaling molecules, metabolic enzymes and transcription factors. Similar results were obtained in human Kit-225 cells. We are designing cDNA-based microarrays that contain IL-2 and rapamycin sensitive mRNAs and using these arrays to study translation control during cell growth and division.