Messenger RNA binding to the ribosome, the rate-limiting step in eukaryotic protein synthesis, is catalyzed by the eIF-4 group of initiation factors. These factors collectively bind to the m7GTP-containing cap of mRNA and unwind mRNA secondary structure at the expense of ATP. One member of the group, eIF-4 gamma, is the target for proteolytic cleavage during picornavirus infection, an event that is thought to be responsible for the inhibition of host cellular mRNA translation. Human eIF-4 gamma migrates as a cluster of polypeptides in the range of 200-220 kDa during SDS-PAGE, raising the possibility that it is a family of proteins encoded by separate genes. In this study, we present genomic Southern blotting results which indicate that there is only a single gene, here designated EIF4G. Furthermore, we have employed a PCR approach to map EIF4G to chromosome 3q27-qter.