While bone marrow transplants (BMT) from related or unrelated donors can cure myeloma, their effectiveness is limited by the side effect of graft-versus-host disease (GVHD). Immune responses by T lymphocytes given later to “mixed chimeras” created with milder BMTs can eliminate malignant cells without causing GVHD. We propose studies to understand why this immune response only attacks host cells in blood, marrow and lymph without attacking the GVHD target issues. These studies will advance the clinical use of his approach to curing myeloma without GVHD, which we have already begun to test in myeloma patients.