Multiple myeloma, a disorder typically accompanied by monoclonal immunoglobulin excess and hypogammaglobulinemia was evaluated to delineate the status of T cell regulation on malignant B cell proliferation. Intact T cells and T cell subsets previously noted by us to be suppressor (T gamma) and helper (T non-gamma) were isolated from 10 controls and 10 myeloma patients. Various concentrations of control and patient T cell subsets were mixed with control and patient B cells and stimulated with PWM. T cell effect on B cell proliferation as measured by [3H]thymidine incorporation was then determined. Myeloma T gamma cells were more effective than control T gamma cells in suppressing control or myeloma B cell [3H]thymidine incorporation. Interestingly, myeloma B cells, when added to myeloma T gamma cells, were suppressed to a greater extent than were control B cells when mixed with a similar concentration of myeloma T gamma cells. These in vitro studies suggest a complexity of B and T cell abnormalities in multiple myeloma; first, the myeloma B cells are extremely sensitive to T gamma cell suppression, and second, myeloma T gamma cells have excessive suppressor capacity. It is yet unclear whether these results are associated with an immunoregulatory response to this malignancy or represent part of the basic disease process.