The Tupaia herpesviruses (THVs) have been isolated from malignant lymphoma tissue cultures and from degenerating lung and spleen cell cultures of tree shrews (Tupaia spp.). Recently we succeeded in the localization of the gene locus of the THV DNA polymerase (DPOL) gene within the viral genome. Based on these results the highly conserved gene cluster of herpesviruses encoding the DPOL, the glycoprotein B (gB), a probable processing and transport protein (PRTP), and the major DNA binding protein (DNBI) was characterized in the genome of THV strain 2 (THV-2) in its entirety. The complete nucleotide sequence of the gene cluster was determined and it was discovered that the THV-2 gene products are most closely related to the corresponding proteins of mammalian cytomegaloviruses. The transcriptional activity of the four genes was confirmed by amplification of a part of the corresponding mRNAs obtained from infected cell RNA by RT-PCR. The homology values and the overall structure of the gene cluster, that shows specific colinearity with the corresponding clusters of the mammalian cytomegaloviruses, is further evidence that THV-2 is a member of the subfamily Betaherpesvirinae.