Restriction of poliovirus replication to a few sites in the infected primate host appears to be controlled by the expression of viral receptors. To learn more about these binding sites and their role in viral tissue tropism, cDNA clones encoding functional poliovirus receptors were isolated. The predicted amino acid sequence reveals that the human poliovirus receptor is an integral membrane protein with the conserved amino acids and domain structure characteristic of members of the immunoglobulin superfamily. Northern hybridization analysis indicates that poliovirus receptor transcripts are expressed in a wide range of human tissues, in contrast to the limited expression of virus binding sites, which suggests that additional factors or modifications of the receptor protein are required to permit poliovirus attachment.