Studies of transcriptional activation by interferons and various 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 required for IL-12 signal transduction. By immunoprecipitation and PCR amplification, a specific consensus sequence for DNA binding of the STAT4 complex was determined. The binding sequence of the STAT4 complex, (T/A)TTCC(C/G)GGAA(T/A), proved to be palindromic and similar to the IFN-gamma activated site (GAS)-like sequence. The first (T/A) and last (T/A) sites of the consensus sequence were critical for the binding affinity of the STAT4 complex.