Joint and bone damage in rheumatoid arthritis is thought to be caused primarily by an imbalance between proteolytic proteinases and their specific inhibitors. Matrix destruction can in part result from the activity of lysosomal cystein proteinases such as cathepsin B and L. Cathepsins usually are determined by enzyme immuno-assay. The aim of this study was the direct determination of synovial thiol-proteolytic activity by spectrofluorimetry using a synthetic substrate (Z-Phe-Arg-NMec) and a cystein proteinase specific inhibitor (E64 = L-trans-epoxy-succinyl-leucylamino-(4 guanidino)-butane). 18 rheumatoid synovial fluids were tested compared to 10 osteoarthritic synovial fluids. Thiol-proteolytic activity appeared higher in rheumatoid arthritis compared to osteo-arthrosis (mean value = 1,311 mU/l vs 156 mU/l, p less than 0.01). Synovial thiol-proteolytic activity is well correlated with synovial elastase-alpha1-proteinase-inhibitor complex. The authors found no correlation with synovial polymorphonuclear count (p = 0.38) nor with clinical and biological parameters of disease evolution. The highest values were observed in patient with radiological signs of joint destruction. Synovial thiol-proteolytic activity might represent the potential destructive evolution of rheumatoid arthritis.