We investigated the dose-response relationship of the intraocular pressure-lowering activity of dorzolamide, a novel topical carbonic anhydrase inhibitor previously known as MK-507. A double-masked, randomized, multicenter study of 113 patients with either primary open-angle glaucoma or ocular hypertension was conducted; dorzolamide (0.2, 0.5, 1, or 2%) was administered three times daily for 14 days. All of the dorzolamide concentrations substantially lowered intraocular pressure from baseline measurements. The percentage change in baseline intraocular pressure with 0.5, 1, and 2% dorzolamide 2, 4, and 6 h after dosing on day 14 ranged from 12.0 to 17.0% on average, which was greater than after treatment with 0.2% dorzolamide. No dose response was seen for 0.5, 1, or 2% dorzolamide. The most frequently reported ocular symptom was transient smarting, which occurred in 35.6-74.1% of every treatment group. Smarting and mild hyperemia were most frequent with 2% dorzolamide (74.1 and 18.5%, respectively). The present results indicate that the 0.5, 1, and 2% concentrations of dorzolamide are almost equally effective and that 2% concentrations may be less well-tolerated than 0.5 or 1% concentrations.