We studied the epithelial healing of denervated corneas in New Zealand albino rabbits with their left trigeminal ganglia surgically amputated. On the 14th day after amputation, the corneas were keratectomized (in 8.5 mm diameter) and documentation of the healing process began. We calculated the epithelial healing rate using simple regression analysis. We observed a mean healing rate of 0.463 +/- 0.059 mm2/hr (mean +/- SE) in the denervated corneas, compared to 0.609 +/- 0.031 mm2/hr in the control corneas; a statistically significant difference of P < 0.001. We performed scanning electron microscopic observation (SEM) at three points; before keratectomy, 48 hrs after keratectomy, and 14 days after keratectomy. SEM observation revealed that, in contrast to the control corneas, the surface of the epithelial cells in denervated corneas appeared rough with numerous exfoliating cells observed. This indicates that the epithelial cells might attach only weakly to the floor in denervated corneas. Transmission electron microscopic observation (TEM) performed at 48 hrs and 14 days after keratectomy also supports this finding. For example, the intercellular space is widened and fewer desmosomes are observed in denervated corneas. Using immunohistochemistry, the surface of the wound bed was covered with fibronectin in a similar fashion to the control. In the late stage, the denervated corneas demonstrated spontaneous epithelial breakdown with 83% of them having persistent epithelial defects. Epithelial healing in the control corneas displayed no abnormal signs. On the 14th day after keratectomy, these eyes were enucleated for immunohistochemistry using bromodeoxyuridine (Brd U) to observe dividing cells.(ABSTRACT TRUNCATED AT 250 WORDS)