The Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus that is implicated in the aetiology of African Burkitt’s lymphoma (BL) and several other cancers of lymphoid/epithelial origin. In vitro, expression of all of the eleven EBV latent proteins or just the oncogenic Latent Membrane Protein 1 (LMP1) can protect BL cells from apoptosis by several stimuli including growth factor deprivation and this is related to the ability to upregulate the expression of several anti-apoptotic 6c/-2-related genes. In this study, it is shown that EBV latent gene expression and in particular LMP1 can induce the upregulation of expression of the anti-apoptotic gene bfl-1 in addition to bcl-2 in BL cells and also that Bfl- 1 expression can not onlt protect BL cells from serum-deprivation-induced apoptosis but also exert a proliferative effect under these culture conditions Bfl-1 has been shown by others to suppress apoptosis and exhibits proliferative and potent cooperative transforming properties. Both increased mRNA stability and increased promoter activity were found to contribute to the effect of LMP1 on bfl-1 expression. The transcription factor NF-kB was shown to mediate the effect of LMP1 on bfl-1 promoter activity in both BL and T cells however, celltype- dependent differences in the regions of the promoter targeted by LMP1 were observed CD40, which engages similar signaling proteins (TRAFs) as LMP1, also stimulates bfl-1 mRNA expression, however, mechanistic similarities and differences were found between the two TNFR family members in this effect LMP1 could also be demonstrated to contribute to activation of the bfl-1 promoter in EBV-immortahsed B lymphoblastoid cell lines (LCLs), however, NF-kB activation may not be the only mechanism regulating bfl-1 promoter activity in different LCLs. A minor but significant finding in this study is that both transcriptional and translational mechanisms are involved in the LMPl-mediated upregulation of bcl-2 expression, with the latter exerting a stronger effect. The upregulation of bfl-1 expression by LMP1 represents the first example of regulation of expression of this anti-apoptotic gene by a viral protein and extends the list of anti-apoptotic proteins whose expression is controlled by LMP1. Protection against apoptosis constitutes an important part of the latent phase of the EBV life cycle, in that it provides a mechanism to ensure life-long viral persistence in the host by mimicking the natural process of selection of B cells into the memory compartment. The regulation of expression of bcl-2-related genes by LMP1 provides an important link between EBV and its cellular survival and growth transforming properties.