The purpose of this study was to determine the percentage of treatment-naive glaucoma patients initially treated with latanoprost monotherapy who do not respond with a clinically meaningful reduction of intraocular pressure (IOP). A database search of previously untreated patients with newly diagnosed primary open angle glaucoma, ocular hypertension or pseudoexfoliative glaucoma initially treated with once-daily latanoprost, 0.005% monotherapy was conducted. Charts were randomly reviewed until 20 patients meeting inclusion criteria were identified. Baseline IOP was compared to IOP measured 1 to 3 months after the initiation of therapy. Intraocular pressure (+/- S.D.) following latanoprost treatment (17.0 +/- 3.5 mm Hg) was significantly (p < 0.0005) less than baseline (23.9 +/- 4.2 mm Hg) in the study population. Based on our criteria of a clinically meaningful decrease in IOP, we identified a subgroup of patients (25%) who were non-responsive to latanoprost monotherapy. Non-responders did not differ from responders with regard to baseline IOP or age. Although latanoprost may be an effective IOP-lowering agent in most patients, there exists a subgroup of patients who are unresponsive. As with any topical glaucoma agent, IOP must be monitored regularly to confirm effectiveness.