STAT family transcription factors regulate gene expression in response to a wide variety of cytokines. A transcription factor designated differentiation-induced factor (DIF), activated by treatment of myeloid cells with the differentiating agents interferon-gamma (IFN-gamma), granulocyte-macrophage colony-stimulating factor (GM-CSF), colony-stimulating factor-1 (CSF-1) or during phorbol ester-induced differentiation, was characterized as a 112kDa protein related to, but not identical with known isoforms of STAT 5. Taken together with previously published results, our data suggest an important function for members of the STAT 5 subfamily in regulating gene expression during the process of myeloid differentiation.