Interleukin-15 (IL-15) has multiple biological properties, including the induction of other cytokine production and the inhibition of T cell apoptosis. Recently, IL-15 was reported to have a major role in synovial inflammation of rheumatoid arthritis, and that it provokes and amplifies the inflammatory process through the activation of TNF-α production. In systemic lupus erythematosus (SLE), the dysregulation of apoptosis and various cytokine production were observed and have been implicated in the pathogenesis of SLE. Thus, we tried to determine serum IL-15 levels in SLE patients and to assess the relationship among IL-15 levels, TNF-α levels and disease activity of SLE. Twenty SLE patients and 10 controls were studied. Paired serum samples were collected from all SLE patients at the time of presentation with active disease and at 4 weeks after institution of treatment. IL-15 levels were determined by ELISA and compared with the disease activity indices in SLE. The disease activity of SLE was measured using the SLE Disease Activity Index (SLEDAI) and laboratory parameters such as circulating immune complex (CIC), C3, C4, anti-DNA antibody, IgG, IgM, and IgA. The IL-15 levels in SLE patients were significantly higher than those of controls (5.38 ± 4.89 vs. 1.04 ± 1.26 pg/ml). However, elevated IL-15 levels did not correlate with the SLEDAI, nor did they correlate with other laboratory activity indices. The changes in serum IL-15 levels did not correlate with the changes in serum TNF-α in the disease course of SLE patients, whereas TNF-α reflected the changes in disease activity of SLE. Serum levels of IL-15 are elevated in SLE patients, but IL-15 did not correlate with the disease activity of SLE. TNF-α production in SLE patients was unlikely to be related with IL-15.