CD4+ T cells that constitutively express CD25 exhibit powerful suppressive properties. Such cells have been denominated regulatory T cells (T(R)). Alterations in T(R)cells are known to cause organ-specific autoimmune disease in animal models. The aim of this work was to quantify CD4+CD25+ T cells in patients with systemic lupus erythematosus (SLE). Thirty untreated patients (ten with active disease) and ten healthy volunteers were studied. Flow cytometry was used to quantify cell populations. CD4+CD69+, CD4+CD25+ and CD4+CD25(bright) cells were considered. Peripheral blood mononuclear cell cultures were performed and supernatants collected for IL-10 and 12 measurement. CD4+CD25+ cells were significantly decreased in patients with active disease when compared to control subjects and patients without disease activity (P<0.001). CD4+CD69+ cells were increased in patients with active disease when compared to controls (P=0.041). Accordingly, CD4+CD25(bright) cells were decreased in patients with active disease compared to healthy subjects (P<0.001). IL-12 production was hampered in cells from patients during periods of active disease when compared to healthy controls and patients during remission (P<0.001). We observed a correlation between decreased T(R)number and reduced IL-12 mononuclear cell production (r=0.362, P=0.05). This work demonstrates that CD4+CD25+ T cells are decreased in patients with clinically active SLE.