Synovial fluids (SF) contain inhibitors capable of neutralizing the activity of proteases secreted by inflammatory cells and fibroblasts. To further define a potential role for SF polymorphonuclear neutrophils (PMN) in mediating joint destruction, peripheral blood PMN were suspended in SF and incubated with reconstituted collagen fibrils. Incubation of PMN-SF mixtures with collagen fibrils precoated with monomeric IgG resulted in significant lysis of the underlying fibrils relative to that seen with uncoated fibrils. Augmented fibril lysis by PMN-SF mixtures in which the PMN were activated with fluid-phase ligands such as phorbol myristate acetate or heat-aggregated IgG was not seen. Lysis of IgG-coated fibrils by PMN-SF was inhibited in the presence of EDTA or sodium azide. PMN-mediated resorption of fibrillar collagen occurred despite the presence of protease inhibitors in the SF at a concentration capable of neutralizing human neutrophil collagenase. These results suggest that the focal release and activation of human neutrophil collagenase during PMN stimulation by tissue-bound immunoglobulins may mediate the resorption of joint tissue collagens in rheumatoid arthritis, even in the presence of protease inhibitors.