Plasminogen activator inhibitor activity was demonstrated in tears of patients suffering from various corneal and conjunctival diseases. Active plasminogen activator inhibitor was also detected by reverse fibrin zymography in tears of a patient suffering from Sjögren's syndrome and in those who underwent eye surgery. Immunoblotting revealed that both type 1 and type 2 plasminogen activator inhibitors may be present in human tears when the epithelial cells of the cornea and conjunctiva are affected and/or the permeability of the conjunctival blood vessels is increased. The molecular weight of inhibitors suggested the simultaneous presence of both free and activator-complexed inhibitors. However, no plasminogen activator inhibitor was detectable in normal human tears, suggesting that the presence of plasminogen activator inhibitors in tears may be associated with the pathological events at the ocular surface.