A20 is an inducible zinc finger protein that confers resistance to tumor necrosis factor alpha cytotoxicity. A survey of various cell lines revealed that A20 was constitutively expressed in Epstein-Barr virus (EBV)-immortalized B-cells. Transfection experiments demonstrated that the EBV latent membrane protein LMP1 induced A20 expression. LMP1 is a transforming protein of EBV that has dramatic effects on cell growth, activation, and survival. An integral membrane phosphoprotein, LMP1 bears no homology to other recognized membrane signaling molecules, and its signal transduction pathway is not known. However, studies using the A20 promoter demonstrated that LMP1 transcriptionally activates the A20 gene through cis-acting kappa B sites. In addition, electrophoretic mobility shift assays confirmed LMP1-inducible binding of an NF-kappa B-like factor to kappa B sequences within the A20 promoter. This is the first report implicating NF-kappa B in signaling by LMP1, a fundamentally important viral transforming protein.