We evaluated the effect of fibronectin (an adhesive protein) and aprotinin (a protease inhibitor) as single or combined topical therapies for primary healing and prevention of recurrent corneal epithelial defects in the rabbit keratectomy wound model. The biological activity of the prepared solutions of rabbit plasma fibronectin (0.6 g/L) was suggested by in vitro assays of rabbit corneal epithelial cell adhesion and gelatin-binding affinity. In the first experiment, we compared fibronectin, albumin (a control nonadhesive protein), and saline. In the second and third experiments, fibronectin supplemented with aprotinin, aprotinin alone, and saline were compared; aprotinin was used at concentrations of 40 and 1000 kallikrein inactivating units (KIU) per mililiter. Our results suggest that topical fibronectin, 0.6 g/L, as well as aprotinin at 40- and 1000-KIU/mL concentrations, given alone or in combination, neither promote corneal epithelial wound healing nor prevent recurrent corneal epithelial defects in rabbit keratectomy wounds.