The aim of this study was to determine the serum interleukin-18 (IL-18) levels in patients with systemic lupus erythematosus (SLE) and to assess their relationship with disease activity. Thirty-five patients with SLE and 35 age- and sex-matched controls were enrolled in this study. Paired serum samples were collected from all the patients with SLE, both at active stage before treatment and at the stable stage after treatment. The serum IL-18 levels were determined using ELISA and their correlations with the disease activity, measured using the SLE Disease Activity Index (SLEDAI) and laboratory parameters such as anti-dsDNA antibody, CH50, C3, C4, and circulating immune complex levels, were analyzed. The serum IL-18 levels in patients with SLE were significantly higher than those in the controls, particularly when the disease status was active (mean+/-SD: active stage, 721.23+/-360.15 pg/ml; inactive stage, 343.68+/-317.78 pg/ml; controls, 113.98+/-13.22 pg/ml, p<0.05). The IL-18 levels measured at the active stage before treatment correlated well with SLEDAI (r=0.41, p<0.05) and anti-dsDNA antibody titer (r=0.35, p<0.05). When we compared the changes of the IL-18 level and those of parameters reflecting the disease activity between the active stage and the stable stage of the disease, it was found that the changes in IL-18 level correlated well with the changes of SLEDAI score during the patient's disease course (r=0.39, p<0.05). In conclusion, the serum IL-18 levels were elevated in patients with SLE, and these increased levels correlated well with SLE disease activity.