The effects of cetylpyridinium chloride on the trans-corneal potential difference and the surface anatomy of the cornea have been examined. Concentrations of cetylpyridinium chloride from 0.21 mM to 2 mM were used for either 1 or 2 minute exposure times on the in vitro and in vivo cornea for the electrophysiology studies. The potential difference of the in vitro cornea showed a concentration and exposure-time dependent decrease, the in vivo cornea shows a qualitatively similar behaviour although quantitatively less. The fall in potential difference is preceeded by a hyperpolarization. The scanning electromicroscopy reveals a loss of microvilli and microplicae as well as surface pitting, with some exposure of cells underlying the superficial epithelium. These changes occur in a dose-dependent manner. The effect of cetylpyridinium chloride on the cornea is to enhance the permeability of the superficial cells by destroying the cell membranes and causing lysis of the cells.