We studied the effect of topical fibronectin on epithelial wound healing and ulceration in alkali-burned rabbit corneas. After the first 56 hours, fibronectin accelerated complete surface reepithelialization to 4.3 +/- 2.3 days. Control alkali-burned corneas treated with phosphate-buffered saline or albumin did not resurface for 6.7 +/- 3.7 days and 6.2 +/- 2.5 days, respectively. When recurrent epithelial defects occurred, the time required for healing was also significantly accelerated by fibronectin treatment. Corneal ulceration developed in 25 of 28 and 15 of 18 saline and albumin-treated control eyes, respectively; only nine of 18 fibronectin-treated eyes ultimately ulcerated. Immunohistologic studies showed that the initially deposited fibronectin-fibrinogen matrix on the surface of burned corneas had disintegrated by 72 to 96 hours after wounding, corresponding clinically to the time of secondary epithelial breakdown. A prominent fibronectin-fibrinogen matrix remained on the surface of fibronectin-treated corneas, presumably aiding surface reepithelialization and decreasing corneal ulceration.