The authors investigated changes in the ratio of CD4+ to CD8+ T cells (CD4/CD8 ratio) and T-cell activation, indicated by human leukocyte antigen (HLA)-DR expression, in patients with systemic lupus erythematosus (SLE) following treatment. An increase was observed in the CD4/CD8 ratio as well as a decrease in the expression of HLA-DR on T cells with the improvement of clinical manifestations on treatment with steroids or cyclosporine (CSA). In addition, steroid treatment suppressed whereas CSA treatment exerted no perceptible influence on the serum interleukin (IL)-16 level, concurrent with changes in T-cell phenotypes. This indicated that the mechanism of the change in the CD4/CD8 ratio differed depending on the drug, and CD8+ T cells could play an important role in reducing this ratio. The CD4/CD8 ratio and HLA-DR expression may be good indicators of therapeutic efficacy in some SLE patients.