With antigen stimulation, cytokine genes are coordinately expressed in T cells. However, the optimal signals or helper T cell subset specificity for each cytokine gene expression differ. Mechanisms probably exist that transmit extracellular signals into the nucleus, thereby coordinately turning on and off transcriptional machinery in a signal-specific or cell type-specific manner. We compare here the regulation of cytokine genes and discuss possible mechanisms of coordinated and differential regulation of cytokine genes.