PURPOSE: To evaluate the magnitude of the contralateral effect of topically administered β-blockers on intraocular pressure. METHODS: The Ocular Hypertension Treatment Study enrolled 1,636 subjects. Of these, 817 subjects were randomized to receive topical ocular hypotensive medication and 819 subjects were randomized to close observation (i.e., no topical medication). We compared the intraocular pressure of the contralateral eye of subjects at the baseline visit and after an initial one-eyed therapeutic trial of topical β-blockers. We examined differences between baseline and follow-up intraocular pressure in untreated eyes of subjects randomized to close observation. RESULTS: The mean reduction in intraocular pressure in the β-blocker-treated eyes was -5.9 ± 3.4 mm Hg (-22% ± 12%; Student t test, P < .0001). In the contralateral eyes, mean intraocular pressure reduction was -1.5 ± 3.0 mm Hg (-5.8% ± 12%; P<.0001). Of the contralateral eyes, 35% showed a reduction of 3 mm Hg or more, and 10% showed a reduction of 6 mm Hg or more. The contralateral effect of the relatively selective β-blocker betaxolol did not differ from that of any of the nonselective β-blockers. Factors associated with the magnitude of the contralateral effect were the degree of intraocular pressure reduction in the treated eye and baseline intraocular pressure of the contralateral eye. In the close observation group, no significant reduction in intraocular pressure was noted between the baseline and follow-up visit. CONCLUSIONS: The contralateral effect is important in clinical practice and in clinical trials when the hypotensive effect of a topical β-blocker is evaluated by means of a one-eyed therapeutic trial. (C) 2000 by Elsevier Science Inc.