Six epikeratoplasty (EKP) specimens were obtained 1 to 10 months after refractive keratoplasty for aphakia (2 cases), keratoconus (1 case), and myopia (3 cases). The EKP grafts were removed because of postoperative complications such as delayed reepithelialization, lenticule edema, stromal ulceration, graft opacification, and inability to improve vision in a clear graft. The extent of epithelial abnormalities was associated directly with the severity of structural changes in the underlying basal lamina, Bowman's layer, and stroma as evidenced by electron microscopic examination. Epithelial defects were associated with varying degrees of sterile stromal ulceration of the underlying lenticule. In one case, an extensive full-thickness ulceration of the EKP button occurred in the area of persistent epithelial defects and was associated with a major ulceration of the underlying recipient's corneal stroma. Removing the failing button halted the ulcerative process with prompt reepithelialization. In the absence of inflammation and infection, the persistent epithelial abnormalities and defects leading to proteolytic degradation of the EKP buttons constitute an important mechanism of graft failure with major visual consequences and possibly irreversible ocular damage.