Certain antisera to immunoglobulins [Ig] containing .kappa.-chains show the presence of antibodies that cross-react with [human .beta.2-microglobulin. This was most apparent with an antiserum made to highly purified F(ab) fragments of Fr II .gamma.-globulin. These cross-reactive antibodies caused positive fluorescence and cytotoxicity reactions with a variety of cell types including T [thymus-derived] cells. These reactions were completely removed by absorption with highly purified .kappa.-chains but not with .lambda.-chains or .lambda. Ig. .beta.2-Microglobulin preparations also absorbed or inhibited the special cellular reactivities. HLA-bound .beta.2-microglobulin was apparently more efficient in this respect. The possibility is discussed that similar cross-reactive antibodies may have been involved in some previous studies of inhibition of T cell function by Ig antisera.