The type I IFNs (IFN-and IFN-) were first characterized as cytokines capable of inducing an antiviral state in sensitive target cells (1). They were originally classified as leukocyte IFN and fibroblast IFN, respectively, to designate their distinct presumptive cellular origins. This designation has been replaced by a more precise nomenclature, based on molecular characterization after the isolation, cloning, and sequencing of the IFN multigene family. The originally detected IFN-activity is encoded by a multigene family of closely related and clustered genes, while IFN-is encoded by a single, somewhat more distantly related gene. It has also become clear that type I IFNs can be synthesized by many, if not all, nucleated cells, just as virtually all nucleated cells have the capacity to respond to secreted IFN to induce an antiviral state. This ability of most cells to secrete and respond to IFN makes the IFN system a powerful first line of defense against pathogens and an essential component of innate immunity (2, 3). IFNs induce more than just antiviral functions, also possessing potent immunomodulatory activities (4). These immunomodulatory effects allow IFNs to serve as a link between innate and adaptive immunity. There is also increasing evidence that they function in a constitutive mode to maintain homeostasis, particularly in the hematopoietic system (5–7). This latter function appears to be a priming effect that maintains target cells in a state of readiness (8). The response to continuous, low-level basal IFN production increases the abundance of a variety of cytokine and pathogen signaling components, potentiating a more rapid and robust response to subsequent activating signals, including the production of IFN itself.