Cytokines and growth factors regulate multiple aspects of cell growth through their interactions with specific receptors. These receptors initiate signals di rected at both the cytoplasmic and the nuclear compartments. Many of the nuclear signals culminate in the induction of new genes. Characterization of the ability of IFN-a. to rapidly induce new genes has led to the identification of a new signaling paradigm, the JAK-ST AT (Signal Transducers and Activa tors of Transcription) pathway. In the IFN-a. pathway, two receptor associated tyrosine kinases from the JAK family, Jald and Tyk2, mediate the activation of two latent cytoplasmic transcription factors, Statl and Stat2. More recent studies have not only determined that this pathway is used extensively, but have led to the identification of additional components (eg, Jak2, Jak3, Stat3, Stat4, Stat5, and Stat6). This review will examine how these components mediate the transduction of signal directly from receptor to nucleus.