Antisera raised against idiotypic determinants of myeloma proteins and macroglobulins have been used to differentiate peripheral blood lymphocytes populations from individual patients. I.D.-positive lymphocytes not resembling plasma cells have been regularly found in peripheral blood in these diseases. This lymphocyte population is heterogeneous with respect to non-tumor-specific surface markers, such as SRBC-, Fc- and C-receptors. Tumor specific idiotypic determinants will thus allow a more correct recognition of the total tumor cell compartment in these diseases.