This prospective, multicenter, double-masked, placebo-controlled study evaluated the safety and efficacy of brinzolamide 1% ophthalmic suspension (Azopt) when used adjunctively with open-label timolol maleate 0.5% (Timoptic). One-hundred-thirty-two patients requiring an adjunctive therapy to timolol 0.5% for the treatment of open-angle glaucoma or ocular hypertension were randomized to receive brinzolamide or placebo three times daily (t.i.d.) in addition to timolol 0.5% twice daily (b.i.d.) for 3 months. Qualifying intraocular pressure (IOP) on timolol 0.5% b.i.d. was 24-36 mm Hg in at least one eye at 8:00 A.M. and 21-36 mm Hg at 10:00 A.M., with no greater than a 5-mm Hg difference between eyes, during two eligibility visits separated by at least 7 days. Treatments were compared using a repeated-measures analysis of variance. Adjunctive therapy with brinzolamide resulted in clinically and statistically significant reductions in IOP from the timolol baseline at all visits. IOP changes from a diurnal baseline ranged from -3.3 mm Hg to -4.1 mm Hg for brinzolamide (N = 53) compared with -0.9 mm Hg to -2.5 mm Hg for placebo (N = 55). Abnormal taste (7.7%) and transient blurred vision (6.2%) were the most frequently reported adverse events. No clinically significant differences in the incidence or severity of ocular signs, visual acuity, cup/disk ratio, or parameters studied on dilated fundus examination were observed between treatment groups. Brinzolamide 1% t.i.d., used adjunctively with timolol 0.5% b.i.d., is safe and well tolerated, and produces clinically and statistically significant additional IOP reductions.