A placebo-controlled, prospective study was undertaken to determine whether apraclonidine has an additive effect in eyes treated with timolol and pilocarpine. Twelve patients with primary open-angle glaucoma while on continuing therapy with timolol 0.5% twice daily and pilocarpine 4% four times a day in both eyes for 3 months were included in the study. A single drop of apraclonidine 1% or placebo was added to treatment with timolol and pilocarpine. Intraocular pressure (IOP) was measured on both days before a single drop of test medications in both eyes as well as 2,4,6, 8 and 12 h later. The fall in IOP with apraclonidine was significantly greater than with placebo at all time intervals (p < 0.05). This study suggests that apraclonidine provides an additive IOP-lowering effect to timolol and pilocarpine for at least 12 h after single-drop applications.