The morphologic effects on rabbit corneal endothelium of several common ophthalmic vehicle constituents were examined following subconjunctival administration. Profound dose-dependent changes consisting of intercellular vacuolization and thickening of the endothelial layer were noted within 1 day following administration of solutions that contained sodium bisulfite or methylparaben and propylparaben. These changes persisted for at least 5 days except in those eyes treated with the lowest concentration of sodium bisulfite. In contrast, administration of sodium citrate and creatinine or unpreserved normal saline resulted in only minimal effects. These changes are of concern because these agents are present in many preparations used to treat a wide variety of eye diseases.