Background: Increased apoptosis may induce autoimmune conditions. Apoptosis is induced by binding of death receptor ligands, members of the tumour necrosis factor (TNF) superfamily, to their cognate receptors. The Fas - Fas ligand pathway has been studied extensively in relation to systemic lupus erythematosus (SLE). However, other death pathways are also considered important. TNF related apoptosis inducing ligand ( TRAIL), another ligand of the TNF superfamily, induces apoptosis in sensitive cells. Objective: To assess soluble (s) TRAIL concentrations in sera of SLE patients. Methods: 40 SLE patients were studied ( 20 with active and 20 with inactive disease). Serum sTRAIL concentrations were measured by a solid phase sandwich enzyme linked immunosorbent assay. Levels in SLE patients were compared with those in patients with rheumatoid arthritis (n = 20), Wegener's granulomatosis ( n = 20), and healthy controls ( n = 20). Results: Mean (SEM) serum sTRAIL concentration in SLE patients (936.0 (108.2) pg/ml) was higher than in healthy controls (509.4 (33.8) pg/ml; p< 0.01) or in disease control patients with rheumatoid arthritis (443.8 (36.1) pg/ml, p< 0.001) or Wegener's granulomatosis (357.1 (32.2) pg/ml; p< 0.001). The mean serum sTRAIL concentration was 1010.2 (168.0) pg/ml for patients with inactive disease and 861.8 (138.7) pg/ml for those with active disease. sTRAIL values were not correlated with specific manifestations of the disease, such as leucopenia or lymphopenia, or with SLE disease activity index. Conclusions: Serum sTRAIL concentrations are increased SLE patients. This seems to be disease specific and could indicate a role for TRAIL in SLE pathophysiology.