To elucidate the role of genetics in familial multiple myeloma, two sisters having plasma cell dyscrasia were studied. The women were 58 and 56 years old, and the diagnoses were made 22 months apart. Specific antisera for patient 1's lambda light chains produced in rabbits had no cross-reactivity with her sister's lambda light chains. Karyotypic analysis by G.T.G. banding revealed abnormalities in both patients, but no common abnormalities. HLA typing disclosed identical tissue types (AW24, A26, B13, BW55). An immunologic epidemiologic study performed on 26 family members, encompassing four generations, disclosed no additional cases of paraproteinemia.