Multiple myeloma is a bone marrow cancer that responds poorly to traditional chemotherapy. TRAIL is a protein that kills cancer cells without affecting normal cells. As I have demonstrated, TRAIL is effective against multiple myeloma cells, even those that do not respond to current chemotherapy, yet does not cause their serious side effects. A Phase I clinical trial of TRM-1, a novel monoclonal antibody that mimics the actions of TRAIL, will soon begin in our institute. In this proposal I will define the effects of TRM-1 on multiple myeloma cells, alone or in combination with other drugs.