This is a collaborative project, focused on the immune effector mechanisms that prevent the proliferation of EBV-carrying cells in man. It involves a comparative study of immunodeficient patients with a high EBV-load, with and without EBV-carrying lymphoproliferative disease. The former group includes the X-linked lymphoproliferative syndrome (XLP) "lymphomas" in renal transplant recipients and various other immunodeficiencies, and the chronic mononucleosis. The latter group consists of Hodgkins and non-Hodgkins lymphoma and CLL patients in remission with exceptionally high anti-EBV (VCA) titers. Effector mechanisms analyzed include natural killer, interferon boosted killer, EBV specific T-cell, antibody dependent lymphocytotoxicity and humoraL EBV-antibody responses. EBV genomes in diseased tissues will be detected by two different methods of nucleic acid hybridization. The results are expected to illuminate the following two questions: a) What immune effector mechanisms are responsible for normally maintained latency of EBV-infected B-lymphocytes in healthy persons? b) Which of the various lymphoproliferative conditions observed in immunodeficient patients are due to EBV?