A 0.1% all-trans-retinoic acid in petroleum-base ointment was applied daily in eight normal rabbit eyes. Epithelial samples were collected from the cornea and limbus of six rabbits by impression cytology at 3- to 4-day intervals. Cytological changes were followed for 21 days and the eyes subsequently harvested for histochemical, scanning electron microscopic (SEM), and transmission electron microscopic (TEM) analysis of corneal and limbal structures. Two rabbits were treated with 0.1% all-trans-retinoic acid for 24 days without impression cytology until the 21st day. On the 24th day these eyes were harvested for similar studies. Impression cytology studies of the corneal epithelium demonstrated perinuclear halos and vacuolization of the cytoplasm. Additionally, vacuolization of the cytoplasm was observed by TEM, with attendant extrusion of the cytoplasmic contents and a subjective increase in surface microvilli as seen by SEM. Histochemical analysis revealed mucinlike staining of the corneal epithelium.