The crystal structure of interferon-γ bound to the extracellular fragment of its high-affinity cellsurface receptor reveals the first view of a class-2 cytokine receptor-ligand complex. In the complex, one interferon-γ homodimer binds two receptor molecules. Unlike the class-1 growth hormone receptor complex, the two interferon-γ receptors do not interact with one another and are separated by 27 Å. Upon receptor binding, the flexible AB loop of interferon-γ undergoes a conformational change that includes the formation of a 310 helix. © 1995 Nature Publishing Groups. All Rights Reserved.