Studies of transcriptional activation by interferons and a variety of cytokines have led to the identification of a family of proteins that serve as signal transducers and activators of transcription (STAT). STAT4 is phosphorylated following interleukin (IL)-12 stimulation and is essential for IL-12 signal transduction. The human STAT4 cDNA was cloned, and both STAT4 and STAT1 genes were mapped to human chromosome bands 2q32.2-->q32.3 by fluorescence in situ hybridization. These results suggest that STAT4 and STAT1 may have arisen via a tandem gene duplication. However, human STAT1 is expressed ubiquitously, whereas human STAT4 is expressed in several tissues including spleen, heart, brain, peripheral blood cells, and testis.