Endemicity of Burkitt's lymphoma (BL) coincides with profusion of a plant Euphorbia tirucalli in tropical Africa. E. tirucalli contains 4-deoxyphorbol ester that enhances Epstein-Barr virus (EBV) infection of B lymphocytes. In this study, we found that 4-deoxyphorbol ester reduced EBV-specific cytotoxic T-cell function. Furthermore, the B lymphocytes dually exposed to EBV and 4-deoxyphorbol ester were resistant to EBV-specific T cell cytotoxicity, through down-regulation of latent membrane protein 1 (LMP1), the major target to EBV-specific cytotoxic T-cells. These immunologic findings strengthen the notion that E. tirucalli may be an important environmental risk factor for the genesis of African BL.