Epstein-Barr virus (EBV) is the human prototype of a family of closely related herpesviruses of Old World primates. These agents probably evolved and spread among the Old World primates since the divergence of apes from monkeys about 30 million years ago. Although the DNAs of the EBV family have no sequence homology to other herpesviruses, there are some features in common with other herpesviral genomes. EBV DNA is unusual in having five tandem direct repeat elements which divide the genome into five unique sequence domains. The tandem direct repeats at the ends of the linear virion DNA probably mediate circularization of the viral DNA to form the circular episomal viral DNA which is characteristic of EBV-infected cells. In latent transforming infection, messenger RNAs are encoded by three widely separate regions of the EBV genome. The remainder of the viral genome encodes many RNAs and proteins which are expressed in productive infection. Early and late viral genes are intermixed along the full length of EBV DNA.