Monoclonal antibodies to known surface antigens on B cells and on resting and activated T cells of various types were used in several approaches to examine the specificity of IgM antilymphocyte antibodies in systemic lupus erythematosus (SLE). Surface determinants that were sought included: T3, T11, Leu-1, Leu-8 (pan-T); T4, T8 (T subset); beta 2-microglobulin (beta 2m); L243, Leu-10 (DR and DS/DC framework, respectively); anti-Tac (interleukin-2 receptor); 5E9 (transferrin receptor); and 4F2, AA1 (other activation antigens). The first strategy was based on inhibition of rosette formation between mouse monoclonal antibody-coated targets and anti-mouse IgG-coated erythrocytes by SLE sera, either directly at 4 degrees C or after modulation of IgM antilymphocyte antibody-reactive target cell antigen at 37 degrees C. Significant rosette inhibition, defined as greater than 2 standard deviations from the mean value for 10 control sera, was seen only for beta 2m (13 of 20 SLE sera were positive; inhibition = 15-58%). Next, relative fluorescence intensity of lymphocyte staining by monoclonal antibodies was assessed by flow microfluorometry after preincubation of cells with SLE serum at 4 degrees C or after modulation of SLE antibody-reactive antigen. Modulation markedly reduced or eliminated SLE antilymphocyte antibody IgM staining. Except for beta 2m, neither cold nor warm temperature preincubations altered the relative fluorescence intensity for the known surface antigens. These data confirm anti-beta 2m as a common antibody specificity in SLE and suggest that antilymphocyte antibodies in this disorder are not directed to Ia or to certain other defined lymphocyte antigens of functional interest.