Herpesvirus saimiri(saimiriine herpesvirus 2) is the classical prototype of the γ2–herpesviruses or rhadinoviruses, which also contains a human member, the Kaposi's sarcoma–associated herpesvirus. The T–lymphotropicHerpesvirus saimiriestablishes specific replicative and persistent conditions in different primate host species. Virtually all squirrel monkeys (Saimiri sciureus) are persistently infected with this virus. In its natural host, the virus does not cause disease, whereas it induces fatal acute T–cell lymphoma in other monkey species after experimental infection. The virus can be isolated by cocultivation of permissive epithelial cells with peripheral blood cells from naturally infected squirrel monkeys and from susceptible New World monkeys during the virus–induced disease. Tumour–derived andin vitro–transformed T–cell lines from New World monkeys release virus particles.Herpesvirus atelesis a closely related virus of spider monkeys (Atelesspp.) and has similar pathogenic properties toHerpesvirus saimiriin other New World primate species.Similar to other rhadinoviruses, the genome ofHerpesvirus saimiriharbours a series of virus genes with pronounced homology to cellular counterparts including a D–type cyclin, a G–protein–coupled receptor, an interleukin–17, a superantigen homologue, and several inhibitors of the complement cascade and of different apoptosis pathways. Preserved function has been demonstrated for most of the homologues of cellular proteins. These viral functions are mostly dispensable for the transforming and pathogenic capability of the virus. However, they are considered relevant for the apathogenic persistence ofHerpesvirus saimiriin its natural host. A terminal region of the non–repetitive coding part of the virus genome is essential for pathogenicity and T–cell transformation. Based on the pathogenic phenotypes and the different alleles of this variable region, the virus strains have been assigned to three subgroups, termed A, B and C. In the highly oncogenic subgroup C strains, the two virus genesstpCandtipare transcribed from one bicistronic mRNA and are essential for transformation and leukaemia induction.Cfils the typical criteria of an oncogene; its product interacts with Ras and tumour necrosis factor–ssociated factors and induces mitogen–activated protein kinase and nuclear factor kappa B activation. Tip interacts with the RNA transport factor Tap, with signal transduction and activation of transcription factors, and with the T–cellular tyrosine kinase Lck, which is activated by this interaction and phosphorylates Tip as a substrate.It is of particular interest that certain subgroup C virus strains such as C488 are capable of transforming human T lymphocytes to stable growth in culture. The transformed human T cells harbour multiple copies of the viral genome in the form of stable, non–integrated episomes. The cells express only a few virus genes and do not produce virus particles. The transformed cells maintain the antigen specificity and many other essential functions of their parental T–cell clones. Based on the preserved functional phenotype of the transformed T cells,Herpesvirus saimiriprovides useful tools for T–cell immunology, for gene transfer and possibly also for experimental adoptive immunotherapy.