Recent animal studies have shown that CD4+CD25+ T cells play a crucial role in the suppression of the immune response and that depletion of this subset of T cells might lead to development of autoimmune diseases. The aim of the present study was to investigate the levels of CD4+CD25+ T cells in the peripheral blood of patients with systemic lupus erythematosus (SLE). Ninety-four SLE patients, 52 patients with rheumatoid arthritis (RA) and 50 age- and gender-matched healthy individuals were enrolled in the study. A flowcytometric method was applied in the measurement of CD4+CD25+ T cells. The results showed that patients with SLE had statistically lower levels of CD4+CD25+ T cells than did normal controls, when expressed as either percentages of peripheral blood mononuclear cells (PBMCs) (mean ± SD, 8.49 ± 6.36 versus 11.11 ± 4.58%, P < 0.05) or absolute cell numbers (98.77 ± 97.52 versus 213.93 ± 104.52 cells/mm3, P < 0.05). In terms of CD25brightCD4+ T cells, defined as having a fluorescence intensity of CD25 expression exceeding 100, SLE patients still had significantly lower levels than did normal controls expressed as percentages of PBMCs (1.76 ± 1.32 versus 3.73 ± 1.30%, P < 0.05). No significant differences could be found between RA patients and normal controls. The overwhelming majority of CD4+CD25+ T cells belonged to CD45RO+ cells and most did not express the CD69 molecule. Although decreased CD4+CD25+ T cells were found in SLE patients, we failed to find a significant correlation between the levels of CD4+CD25+ T cells and disease activities of SLE. To the best of our knowledge, this is the first study to demonstrate that patients with SLE had decreased CD4+CD25+ T cells. However, the exact role of the decreased CD4+CD25+ T cells in the pathogenesis of SLE remains to be elucidated.