A role of natural regulatory CD4+CD25+ T cells in peripheral tolerance has been established, but a causative role of these cells has not been proved in human autoimmune diseases. Functional alterations have been reported in arthritis and contradictory results have been published in systemic lupus erythematosus (SLE). In this study, the CD4+CD25+ T cell function was studied in 12 SLE patients (6 with only antimalarials and 6 also with corticoids treatment) in parallel to 12 healthy controls. CD4+CD25- T cells were cocultured with allogenic monocyte derived dendritic cells (MDDC) and CD4+CD25+ T cells were added. Proliferation was measured by [3H]-thymidine incorporation and TNFalpha secretion was assessed by ELISA. A better anti-proliferative function of CD4+CD25+ T cells was found in patients than in controls (p=0.009), whereas higher TNFalpha secretion was found in patients (p=0.028). There were no significant differences regarding treatment. In summary, CD4+CD25+ T cells from SLE patients showed an undamaged anti-proliferative function. Our results and other authors' have not proved a SLE causative role for CD4+CD25+ T cells. The reduced inhibitive function on TNFalpha secretion found in patients could have some implications in lupus pathogenesis.