Despite extensive studies, the structure of the erythropoietin receptor remains little understood. cDNAs encoding the human and murine erythropoietin receptors have been cloned and the structure of these proteins is discussed. Although the proteins encoded by these cDNAs play key roles in erythropoietin binding and in erythropoietin signal transduction, increasing evidence strongly suggests that the erythropoietin receptor is a multimeric complex. The murine erythropoietin receptor has been solubilized under mild conditions and the molecular mass of the native receptor has been shown to be significantly higher than the molecular mass of the cloned chain. Cross-linking experiments have revealed the presence of three proteins covalently bound to erythropoietin by the cross-linking reagents; however, only one of them seems to derive from the cloned chain. Moreover, functional evidence also suggests the presence of other erythropoietin receptor subunits.