The authors compared the additive intraocular pressure (IOP)-lowering effects of two different topical medications, apraclonidine hydrochloride and dipivefrin hydrochloride, when used in conjunction with timolol maleate. Eighteen patients with elevated IOPs entered a randomized, double-masked, cross-over study. Each used apraclonidine 1.0%, dipivefrin 0.1%, or placebo, twice daily for 3 weeks each, in addition to timolol 0.5% twice daily. Only apraclonidine produced a significant additional IOP lowering over timolol treatment alone at all time intervals (P less than 0.001). Its additive effect was significantly greater than that seen with dipivefrin at all time intervals (P less than 0.01), with the exception of day 22 (P = 0.061). No significant change in pulse rate or blood pressure was seen during apraclonidine administration. Apraclonidine may be a useful adjunctive agent in patients with poorly controlled glaucoma.