Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown origin affecting all the organ systems. Apart from genetic and environmental factors, autoantibody and immune complex deposition as well as cytokine imbalances contribute to immune dysfunction. Interleukin-9 (IL-9) is a T cell-derived factor preferentially expressed by CD4(+) T cells and it has been characterized in human and murine systems. IL-9 targets cells of the lymphoid, myeloid and mast cell lineages, and is likely to contribute to the development of allergic and autoimmune diseases such as asthma, arthritis, multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). Nevertheless, until recently there have been no studies on its role in SLE in humans. In the present study, the mRNA and serum IL-9 levels in the peripheral blood of SLE patients and healthy controls were assessed using real-time PCR and enzyme-linked immunosorbent assay (ELISA), respectively. Flow cytometry was used to analyze the percentages of CD4(+)IL-9(+) T cells in SLE patients. Moreover, differences between the groups and the effect of glucocorticoids were analyzed. The results showed that the plasma concentration and mRNA levels of IL-9 were significantly elevated in SLE patients compared with the healthy controls. The percentages of CD4(+)IL-9(+) T cells were also increased in SLE patients. In addition, serum IL-9 levels and the percentages of CD4(+)IL-9(+) T cells were correlated with the SLE disease activity index (SLEDAI). Additionally, the percentages of CD4(+)IL-9(+) T cells and serum IL-9 levels in 8 untreated active SLE patients were decreased at 1, 2 and 3 weeks after treatment with methylprednisolone. In conclusion, we provide evidence that IL-9 is increased in SLE patients. Moreover, it is described for the first time that high expression of IL-9 levels and the percentages of CD4(+)IL-9(+) T cells correlate with disease activity and severity. This suggests an important role of IL-9 in the pathogenesis of SLE.