A cDNA encoding the human interferon-y receptor was isolated from a kg111 expression library using a poiyclonal antireceptor antiserum. The gene for this receptor was identified in a cosmid library and transfected lnto mouse ceils. The human interferon-y receptor expressed in mouse cells displayed the same binding properties as in human cells. However, transfected ceils were not sensitive to human IFN?, sug gesting the need for species-specific cofactors in receptor function. As inferred from the cDNA sequence, the human interferon7 receptor shows no similarities to known proteins and represents a novel transmembrane receptor. It is most likely the product of a single mRNA and a gene located on chromosome 6%