The effects of fibronectin and epidermal growth factor (EGF) on the migration of corneal epithelial cells in situ were investigated. When rabbit corneal blocks were cultured in serum-free medium with fibronectin or EGF, corneal epithelial cells migrated on the cut surface of the stroma. Histological and electron microscopic studies revealed that the leading edge of the fibronectin-treated cornea was thin, single-layered epithelium, whereas the leading edge of the EGF-treated cornea was a hypertrophic, multilayered epithelium. By autoradiography with 3H-thymidine, the authors observed that EGF stimulated corneal epithelial cell proliferation; however, fibronectin had no effect on cell proliferation. These results demonstrate that fibronectin and EGF enhance migration of corneal epithelial cells in different ways: Fibronectin facilitates sliding of epithelium, whereas EGF increases cell proliferation.