PURPOSE: To compare the 24-hour diurnal ocular hypotensive efficacy of two dosing regimens of latanoprost, once daily (8 AM or 10 PM), vs timolol maleate, twice daily. METHODS: We measured six diurnal intraocular pressure curves (6 AM, 10 AM, 2 PM, 6 PM, 10 PM, and 2 AM) in one randomly selected eye of 34 Greek patients newly diagnosed with primary open-angle glaucoma. The first diurnal curve was an untreated baseline. Patients began taking timolol 0.5%, twice daily, for 2 months. Patients were randomly assigned to latanoprost 0.005% given at 8 AM or 10 PM for 1 month and then changed to the other dosing regimen for 1 month. A diurnal curve was performed after each dosing period. RESULTS: The baseline diurnal pressure for all 34 subjects was 23.1 +/- 3.7 mm Hg. The average intraocular pressures at 6 AM for patients who were given latanoprost in the evening (17.9 +/- 2.9 mm Hg) was statistically lower than that in patients given timolol solution (20.1 +/- 2.5 mm Hg, P = .003); however, patients who were given timolol demonstrated a similar diurnal intraocular pressure (19.1 +/- 2.8 mm Hg) to both morning (18.8 +/- 3.7 mm Hg) and evening doses (18.8 +/- 3.6 mm Hg) of latanoprost (P = .329). When the two latanoprost dosages were compared directly, evening administration provided a statistically lower intraocular pressure at 10 AM (P = .0001) and morning administration at 10 PM (P = .0001). This study had an 80% power to exclude a 1.2-mm Hg difference between groups. CONCLUSIONS: This study indicates that in a small population, both latanoprost and timolol are effective in lowering intraocular pressure throughout a 24-hour period; however, latanoprost is most effective in the 12-hour to 24-hour period after administration. (Am J Ophthalmol 1999;128:15-20. (C) 1999 by Elsevier Science Inc. All rights reserved.)