CD30/CD30L and CD40/CD40L are molecules from the tumor necrosis factor (TNF) superfamily. They have a major effect on communications between the B and T cells, which leads to control of maturation, proliferation, and apoptosis of those cells. The aim of this study was to compare the levels of a soluble form of CD30 (sCD30) and a soluble ligand CD40 (sCD40L) in patients with systemic lupus erythematosus (SLE) (n=65) and healthy controls (sCD30 n=20, sCD40L n=10) with other parameters of SLE activity. Patients were divided into subgroups according to presence or absence of lupus nephritis (LN; 33 with LN, 32 without LN). The serum levels of selected parameters were assessed also in the subgroups with low active disease characterized by European Lupus Activity Measure (ECLAM) at most 3(n=29) and active disease with ECLAM more than 3 (n=36). The serum levels of sCD30 were 66.0+/-40.2 UI/ml in the whole group. The mean serum levels were 60.0+/-45.2 UI/ml in the subgroups with LN, 67.1+/-38.9 UI/ml in the subgroup without LN, 80.2+/-51.9 UI/ml in the subgroup with active disease, 55.4+/-24.1 UI/ml in the subgroup with low active disease, and finally, 40.1+/-19.2 U/ml in the controls. Significant differences were found between the SLE patients and controls (p=0.0001) and between the active and nonactive groups (p=0.002). A correlation was found between levels of CD30 and ECLAM (r=0.25, p<or=0.05), SLEDAI (SLE Disease Activity Index) (r=0.25, p<or=0.05), C4 component of the complement system (r=0.24, p=0.02), and anti-C1q antibodies (r=0.42, p=0.0001). The levels of sCD40L were 7.4+/-6.7 ng/ml in whole SLE group, 7.0+/-8.1 ng/ml in the subgroup with LN, 8.0+/-4.9 ng/ml in the subgroup without LN, 7.1+/-5.0 ng/ml in the group of patients with active disease, 7.73+/-7.8 ng/ml in the subgroup with low activity, and 2.96+/-1.39.0 ng/ml in the controls. The difference in sCD40L serum levels between patients with SLE and controls was statistically significant (p=0.02). A correlation was found with the anti-C1q antibodies (r=0.21, p=0.05); no other correlations were found. These findings indicate some potential role of both serum parameters in measurement or SLE disease activity, although their usage in the diagnostic of disease requires further investigation.