To investigate serum levels of soluble Fas (sFas), soluble Fas ligand (sFas-L), and matrix metalloproteinase-3 (MMP-3) in patients with active untreated adult onset Still's disease (AOSD). Serum levels of sFas, sFas-L, and MMP-3 were determined by enzyme-linked immunosorbent assays in 20 patients with active untreated AOSD, 20 patients with active rheumatoid arthritis (RA), and 20 healthy controls. Linear regression was used to evaluate the correlation between clinical activity scores and serum levels of sFas, sFas-L, and MMP-3 in AOSD patients. Significantly higher levels of sFas, sFas-L, and MMP-3 in sera were found in active untreated AOSD patients compared to healthy controls. Serum levels of sFas, sFas-L, and MMP-3 correlated well with clinical activity scores of AOSD patients (r=0.467, 0.694, and 0.798, respectively). There was a significant correlation between CRP values and serum levels of sFas-L as well as MMP-3 (r=0.583 and r=0.582, respectively, both p<0.01), and a positive correlation between serum sFas-L levels and serum MMP-3 levels (r=0.726, p<0.001) in AOSD patients. Significantly higher levels of serum sFas-L were found in AOSD patients than in RA patients. Serum levels of sFas, sFas-L, and MMP-3 fluctuated and were found to be parallel to disease activity of AOSD. sFas, sFas-L, and MMP-3, which were significantly elevated in sera of active untreated AOSD patients and paralleled disease activity, may be involved in the pathogenesis of this disease. Further studies are needed to determine the pathophysiologic role of sFas, sFas-L, and MMP-3 in AOSD.