A soluble form of cytotoxic T-lymphocyte-associated antigen-4 (sCTLA-4) was recently found and shown to possess a downregulatory function as a membrane-bound CTLA-4 molecule. The purpose of the study was to investigate the expression of sCTLA-4 molecule in patients with systemic lupus erythematosus (SLE). One hundred patients with SLE and 40 age- and sex-matched healthy individuals were enrolled in the study. The results showed that patients with SLE have significantly higher levels of sCTLA-4 in sera than healthy controls (21.6 +/- 12.3 ng/ml versus 5.9 +/- 5.4 ng/ml, P < 0.001). Increased expression of sCTLA-4 mRNA in peripheral blood mononuclear cells (PBMCs) was also found in SLE patients. However, we could not find a statistically significant correlation between the serum levels of sCTLA-4 and lupus disease activities. The reported CTLA-4 gene polymorphism in promoter region at position -318 did not affect the levels of sCTLA-4. To the best of our knowledge, this is the first report showing that patients with SLE have increased sCTLA-4 expression. However, the mechanism and role of increased sCTLA-4 in the pathogenesis of SLE remains elucidated.