Formation of epiretinal membranes occurs in proliferative vitreoretinopathy, macular pucker and after penetrating trauma. Epiretinal membrane formation includes cell migration and proliferation, extracellular matrix formation and tissue contraction. Generally in scar tissue formation, the production of new extracellular matrix occurs concomitantly with its proteolytic degradation, resulting in continuous tissue remodelling. The plasminogen activator-mediated proteolytic cascade is an important mechanism for pericellular degradation of the extracellular matrix. Therefore we wanted to study the presence of the plasminogen activator-mediated proteolytic cascade in epiretinal membranes.Specimens of 18 epiretinal and 3 subretinal membranes were obtained during vitreous surgery for retinal detachment with proliferative vitreoretinopathy or macular pucker. Plasminogen activators and plasmin were characterized in frozen sections of epiretinal membranes by in situ zymography and in membrane lysates by zymography. Indirect immunofluorescence staining was performed to localize urokinase in epiretinal membranes.Urokinase was present in 17/21 and tissue-type plasminogen activator in 12/21 of the membranes studied. Active plasmin was not detected in the frozen sections of epiretinal membranes. Immunofluorescence staining localized urokinase predominantly in the areas invaded by macrophages and cells of retinal pigment epithelial origin.Our results demonstrate the presence of proteolytic activity in periretinal scar tissue. Urokinase was more consistently present, but smaller amounts of tissue-type plasminogen activator were also found in the specimens. These results indicate that continuous tissue remodelling with simultaneous extracellular matrix production and breakdown regulates the growth of epiretinal membranes.