Steroid hormones have long been known to have a profound influence on the immune system. Although the functions of these nuclear receptors in the development of T cells are fairly well studied, the differential expression of these receptors in T helper cells is poorly understood. Here, we investigated the differential expression of nuclear receptors and coregulators in Th1 and Th2 cells by genomewide microarray analysis. The result showed that several nuclear receptors and coregulators are differentially expressed in these cells. The result was confirmed by RT-PCR. The result showed that RXRalpha is highly expressed in Th2 cells. Overexpression of RXRalpha in a Jurkat human T cell line induced IL4 but not IFN-gamma gene expression, suggesting that RXRalpha plays a selective role in Th1 and Th2 differentiation. In summary, these results suggest that Th1/Th2 differentiation may be influenced by differential regulation of nuclear receptors and coregulators.