The Epstein-Barr virus (EBV), carried by the majority of the world's adult human population, is closely associated with three known human diseases; infectious mononucleosis IM), Burkitts lymphoma (BL) and nasopharyngeal carcinoma (NPC). It is now generally accepted that EBV plays an active role in the etiology of BL and NPC rather than simply being a "passenger". Considerable evidence also argues for the participation of "co-factors" in these two diseases. Environmental co-factors appear needed to explain the peculiar geographical distribution of BL. Among various possibilities that must be considered are insect-transmitted agents that could lead to eventual immunosuppression and/or stimulate further proliferation of EBV-transformed cells, thereby permitting an additional cytogenetic evolution towards malignancy. Recent studies have uncovered a possible cytogenetic co-factor in the ethiology of BL; the 8-14 chromosomal translocation. Genetic co-factors, on the other hand, are likely to be involved in the etiology of NCP. EBV is a B-cell associated virus. Carrier lymphoid cell lines obtained either by in vitro "immortalization" of human cord-blood lymphocytes or by explants from IM and African BL donors harbor multiple copies of the EBV genome, and viral genetic sequences have also been directly detected in biopsies of African BL. The state of the viral genomes in the carrier cell appears to be such that some are integrated into the cellular DNA while others exist as free, covalently closed circular molecules.