We recently isolated a cDNA clone encoding the murine erythropoietin (Epo) receptor from a PXM expression library made from uninduced murine erythroleukemia cells. The clone was identified by screening COS cell transfectants for internalization of radiolabeled recombinant human Epo. As inferred from the cDNA sequence, the murine Epo receptor (Epo-R) is a 507 amino acid polypeptide with a single membrane-spanning domain. Extensive homology was found between the Epo-R and the interleukin 2 receptor beta chain, both at the level of amino acid sequence and at the level of regional hydrophobicity.