Relative reactivity of anti-lymphocyte autoantibodies (ALA) from patients with systemic lupus erythematosus (SLE) against CD4+ and CD8+ T cells was studied using C'-dependent microcytotoxicity assay. Of 46 SLE sera screened for anti-T cell autoantibodies, 27 sera (59%) showed significant cytotoxic reactivity. Of these, positive correlation between the titer of anti-T cell antibody and CD4/CD8 killing ratio (p<0.01) was demonstrated. In time course study of individual patients, the CD4/CD8 killing ratio increased and decreased as the disease flared and subsided and was accompanied by parallel changes in the titer of anti-T cell antibody titer. Moreover, as sera were serially diluted, the CD4/CD8 killing ratio decreased in 5 out of 10 sera. These results suggest that discrepancy among reports concerning the subset specificity of anti-T cell antibodies may be due, in part. to differences in the titer of ALA in the sera studied and to the dilution of serum used.