The present study was designed to determine whether the corneal penetration of test compounds is altered in aging. Experiments were carried out by means of passive transport under steady-state conditions using in vitro diffusion cells. Permeabilities of a variety of compounds with different physicochemical properties were measured in young (six weeks) and old (three to four years) intact and denuded (wounded) rabbit corneas. There was a marked difference in penetration of compounds between young and aged corneas. A significant decrease in permeability with age was observed. The degree of difference depended on the lipophilicity and molecular weight of the compound and the integrity of the epithelial cell layer. The difference was more pronounced for large hydrophilic than small lipophilic compounds in the intact corneas. The difference in permeabilities of test compounds between young and old denuded corneas was essentially the same (about 2- fold). These studies provide clues to the fundamental biochemical difference in young and old corneas and better enables the development of rationales for efficient drug and nutrient delivery across the cornea.