Tap water (100 ml/kg) was administered by oral gavage to normal adult rabbits. Significant elevation of the intraocular pressure (IOP), lasting for at least 30 minutes, was observed. Following topical treatment, the IOP was significantly reduced by epinephrine bitartrate, carbachol, isoproterenol bitartrate (Isolevin [Britain]), hexamethonium chloride, propranolol hydrochloride, pilocarpine hydrochloride, and physostigmine salicylate, but not by phenoxybenzamine hydrochloride or atropine sulfate. Oral administration of dichlorphenamide or acetazolamide, three hours prior to "water loading," resulted in a lower IOP than that observed for normal control animals. Based on these data, the water-loading test in rabbits appears to represent a valid procedure for screening drugs with potential antiglaucoma activity.