Objective: To investigate the additive ocular hypotensive effect of latanoprost on the intraocular pressure (IOP) reduction induced by a suboptimal dose of acetazolamide, a carbonic anhydrase inhibitor. Design: A short-term, randomized, placebo-controlled, double-masked study. Participants: Twenty-four patients with glaucoma with elevated IOPs. Intervention: Acetazolamide 250 mg twice daily from day 1 to day 18. Topical 50 mu g/ml latanoprost or placebo eye drops bilaterally instilled once daily from day 4 to day 18. Mean Outcome Measures: IOP, conjunctival hyperemia. Results: The mean IOP of 19.5 mmHg during acetazolamide treatment was further reduced to 16.8 mmHg after topical administration of latanoprost, i.e., a decrease of 2.9 +/- 2.8 mmHg (15%, P < 0.001). Administration of placebo to patients on acetazolamide resulted in an upward drift of 1.3 mmHg (6%, P = 0.03). A modest but statistically significant increase in conjunctival hyperemia was found in the latanoprost-treated group, but did not affect the masking. Conclusions: This short-term study indicates that the combination of topically applied latanoprost and a suboptimal dose of systemic carbonic anhydrase inhibitor is useful in the management of glaucoma.