The recently identified gamma herpesvirus, Kaposi's sarcoma herpesvirus or KSHV, has been associated with multiple neoplasms including Kaposi's sarcoma, non-Hodgkin's lymphoma, Castleman's disease and multiple myeloma. The role of KSHV in transformation is not clear, but clinical data strongly support the role of immunologic competence in controlling KSHV- related disease in transplant or AIDS-related KS. Therefore, characterization of the cellular immune response to KSHV may provide the basis for immunologic interventions to treat and prevent KSHV-related cancer. The identification of KSHV may provide the basis for immunologic interventions to treat and prevent KSHV-related cancer. The identification of KSHV in multiple myeloma bone marrow stromal cells, but not in MGUS or other disorders has provided a highly exploitable target for immune based therapies. The hypothesis that KSHV is linked top multiple myeloma will be analyzed in detail focusing on the characterization of the immune response to KSHV in myeloma to generate specific immunologic strategies to treat and/or prevent this disease. Specifically, we propose. 1. To further define and characterize KSHV in multiple myeloma. 2. To assess CTL response to KSHV in myeloma and the prodromal condition, MGUS. 3. To assess KSHV-specific CD4 helper cell responses in myeloma and MGUS.