A large number of cytokines have been shown to possess a four-helix bundle structure with a unique up-up-down-down connectivity. The receptors for this family of cytokines have been shown to be homologous as well, each possessing two tandem repeats of a fibronectin type III-like domain. The crystal structure of human growth hormone bound to the soluble portion of its receptor has served as the only experimentally-determined example of the interaction between the four-helix bundle cytokines and their receptors: two identical receptor subunits bind to different epitopes on the same growth hormone ligand. We have conducted a series of experiments to determine if this structural paradigm is true for interleukin-4 and interleukin-4 receptor. Native polyacrylamide gel electrophoresis and gel filtration chromatography reveal that interleukin-4 forms a tight 1:1 complex with the system.