Multiple myeloma is a neoplastic disease which was thought to arise from a single plasma cell. Its etiology is unknown. Recent advances in chromosomal analysis have established the presence of a consistent abnormality (a 14q plus translocation) in many patients with malignant disease of the lymphoid system. This abnormality along with a multitude of others has been described in myeloma. Although myeloma is thought to be a disease of the end stage cell of B cell differentiation, the possibility that the neoplastic event occurs in a plasma cell precursor or a cell regulating B cell function exists. Our laboratory has devised techniques of separating plasma cells, B and T lymphocytes from bone marrows as well as the peripheral blood in patients with multiple myeloma. We propose to isolate these individual cell populations from patients with myeloma and subject each of them to chromosomal analysis to establish the cell or origin of the neoplastic crest. If consistent abnormalities in B and/or T lymphocytes are found, then abnormal early B cell function or regulation must be seriously considered in the etiology of this disease.