Interferon-gamma (IFNγ) is an important immunomodulatory cytokine produced by activated T cells and NK cells that plays a pivotal role in promoting host defense. IFNγ is distinguished from IFNα and IFNβ by its ability to regulate a number of immune functions. IFNγ induces its biologic effects by interacting with a specific IFNγ receptor expressed at the cell surface. Recently, IFNγ receptors have been purified from human and murine cells and their cDNAs cloned and expressed. This work has revealed that IFNγ receptors are 90 kDa, single chain glycoproteins that bind ligand with high affinity in a species specific manner. There appears to be only a single type of IFNγ receptor that is expressed on nearly all cell types. Whereas this single polypeptide is sufficient to confer ligand binding and processing activity to transfected cells, a second, as yet undefined, component is required to form a functionally active IFNγ receptor. The identity of this second component is currently being investigated. In addition, recent work has revealed novel structure-function relationships that exist within the IFNγ receptor's intracellular domain. This work has shown that distinct portions of the intracellular domain are differentially responsible for mediating different biologic activities of the receptor.