Ten multiple myeloma (MM) and 5 monoclonal gammopathies of undetermined significance (MGUS) were studied. The mixed lymphocyte reaction (MLR) proliferative response was of the same order of magnitude in MM and in MGUS as in normal controls. Normal results were obtained when pathological lymphocytes were used as either responding or stimulating cells. The addition of monoclonal anti-Ia antibodies completely abrogates the proliferative response as in healthy individuals. These results suggest that the immunological mechanisms supposed to be important in MLR are functionally normal in MM and in MGUS, although both the B and T cell lineages are involved in monoclonal gammopathies.