Elevated intraocular pressure (IOP) has been produced in rabbits upon chronic instillation of corticosteroids. These steroid-induced elevated IOP's were concentration-dependent and were followed by the known systemic toxic effects consisting of weight loss, polyuria, polydipsia and frequent deaths depending on the concentration instilled. The severity of the elevated IOP produced by twice daily instillation of corticosteroids was concentration-dependent as well as dependent on the type of corticosteroid instilled. In this study dexamethasone 21-phosphate and betamethasone 17-valerate produced the severest elevations of IOP in rabbits, whereas hydrocortisone and 11β-hydroxy-6α-methylpregn-4-ene-3,20-dione (medrysone) produced moderate elevation. Approximately three-fourths of the treated animals responded to corticosteroid instillation with IOP elevations, with the responding animals exhibiting various degrees of severity in elevated IOP. The elevated IOP could be reversed by discontinuation of steroid instillation as well as by adrenergic drugs and carbonic anhydrase inhibitors. The IOP effects paralleled the anti-inflammatory potency of the steroids, and all of the steroids evaluated exhibited IOP elevation upon chronic instillation.