Many pathological processes, including rheumatoid arthritis, are associated with the presence of specialised subsets of T helper cells at the site of inflammation. Understanding the genetic program that control the functional properties of Th1 versus Th2 cells may provide insight into the pathophysiology of inflammatory diseases. We compared the gene expression profiles of human Th1 and Th2 cells using high-density oligonucleotide arrays with the capacity to display transcript levels of 6000 human genes. This approach resulted in the identification of more than 200 differentially expressed genes, including genes controlling the different steps of lymphocyte migration and homing1. A subset of these genes was further upregulated by exposure of differentiated Th1 cells to IL-12. Functional assays and in vivo expression of selected genes have validated the biological relevance of this study. Our results provide novel insight into the transcriptional program controlling the differential ability of T helper subsets to traffic and localise to sites of inflammation.