Human herpesvirus 8 (HHV-8) infection is associated with the development of primary effusion lymphoma, Kaposi's sarcoma, and multicentric Castleman's disease. The K1 gene of HHV-8 is expressed in tumor cells as a transmembrane protein with an immunoglobulin-like domain in its ectodomain and an immunoreceptor tyrosine-based activation motif (ITAM). We demonstrated that K1 protein activates nuclear factor-kappa B (NF-κB), and K1 expression in transgenic mice stimulated accumulation of lymphatic cells and development of lymphoma. How K1 blocks apoptosis and induces hyperplasia and lymphomas is not known. We hypothesized that K1 contributes to lymphoma development partly by suppressing apoptosis, and that this suppression combined with its NF-κB activation produces lymphoma.