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The unilateral, topical administration of certain ocular hypotensive agents, notably clonidine, is reported to result in a bilateral decrease in intraocular pressure. It has been previously proposed that such bilateral ocular hypotensive responses may be centrally mediated. However, the possible influence of blood pressure changes on intraocular pressure has remained a complicating factor in determining mechanisms of action. In order to further clarify the potential relationship between systemic blood pressure changes and intraocular pressure, the effects of two systemic antihypertensive drugs were determined in the conscious rabbit. Topical, unilateral administration of either hydralazine or prizidilol did not lower the intraocular pressure of either eye. A bolus intravenous injection of either hydralazine or prizidilol caused substantial systemic hypotension that persisted for at least 3 h, but no decreases in intraocular pressure occurred. These studies indicate that sustained decreases in systemic blood pressure of approximately 15 mm Hg do not result in ocular hypotension.