A prospective, double-masked, randomized study evaluated the effects of unilateral therapy with topical 1% apraclonidine hydrochloride (aplonidine hydrochloride or ALO 2145) in 20 normal volunteers. No medications were applied to either eye during the control day. Following baseline measurements on the day of treatment, one drop of topical 1% apraclonidine hydrochloride was placed on one eye and a placebo (vehicle) was placed on the fellow eye. Intraocular pressure (IOP) measurements, pupil size, blood pressure, and pulse rate were assessed on both days at the baseline and 1, 3, 5, and 7 hours later. The 1% apraclonidine hydrochloride lowered the mean IOP (+/- SD) a maximum of 6.5 +/- 4.3 mm Hg (37.3% +/- 20.4%) from the baseline on the day of treatment. A statistically significant 2.7 +/- 3.4-mm Hg (14.9% +/- 19.0%) mean IOP decrease from the baseline was noted in the contralateral placebo-treated eye. No significant changes in the coefficient of outflow, blood pressure, or heart rate were noted. Eyelid retraction, conjunctival blanching, and mydriasis were frequently noted in eyes treated with 1% apraclonidine hydrochloride.