Dietary vitamin A deficiency in young rabbits caused advanced squamous metaplasia with keratinization of conjunctival epithelium and concomitant reduced paracellular permeability to 3H-mannitol. Both morphologic and permeability changes were reversed with systemic administration of vitamin A. In adult rabbits, vitamin A deficiency caused milder changes of goblet cell loss and increased cellular stratification in conjunction with reduced permeability in the conjunctiva-like epithelium that covers the vascularized cornea after chemical injury with n-heptanol. Topically applied retinoid (tretinoin 0.1%) did not affect the morphology and permeability of the normal corneal or conjunctival epithelium of rabbits that were not vitamin A deficient. These studies showed that altered permeability is associated with the epithelial abnormality during vitamin A deficiency and helped clarify the physiologic function of retinoids in the ocular surface epithelia in the nondeficient state.