In evaluating hypoimmunoglobulinemia in a patient with nonsecretory myeloma, studies of in vitro immunoglobulin synthesis were performed during a 3-year period. Impaired polyclonal response to mitogen stimulation associated with excessive suppressor activity was demonstrable at diagnosis. Despite successful chemotherapy, serum immunoglobulin levels remained depressed with a persistent impairment in polyclonal immunoglobulin synthesis but without evidence for excessive suppression. In nonsecretory myeloma, as in secretory myeloma, a defective B-cell response to differentiation signals may be a contributory mechanism in the hypoimmunoglobulinemia seen in this disease.