Plasmin, a proteolytic enzyme, has been detected in the tears of patients experiencing anterior ocular disease, and during contact lens wear. Using a radial caseinolysis procedure, we examined tear plasmin levels in 66 patients who were wearing soft and rigid lenses for daily and extended wear. Compared to non-contact lens wearers, patients wearing soft and rigid lenses for extended wear were significantly more likely to exhibit tear plasmin activity. Eight hours of open-eye thick HEMA lens wear did not induce tear plasmin activity in a group of 10 subjects. However, significant increases in tear plasmin activity were recorded after short-term (1 hour) eye closure with and without lens wear, and following overnight (8 hours) eye closure without lens wear. Overnight eye closure also resulted in significantly increased numbers of epithelial cells and leucocytes in the tear fluid. Our results suggest that increased tear plasmin activity during extended contact lens wear may be attributable to the effects of eye closure rather than hypoxia or the presence of the contact lens per se.