The long term effects of two dose regimens of latanoprost (PhXA41) administered to eyes concomitantly treated with timolol which had not adequately been controlied by timolol alone were compared. A total of 50 patients, 17 with primary open angle glaucoma and 33 with capsular glaucoma, were recruited from five clinics. All had glaucomatous visual field defects and an intraocular pressure (IOP) of at least 22 mm Hg despite treatment with 0*5% timolol twice daily. Patients were randomised to two treatment groups. In one group 0.006% latanoprost was given twice daily, in the other group placebo was given at 8 am and latanoprost at 8 pm for 3 months, with concomitant timolol treatment in both groups. Average daytime IOP (mean (SD)) at baseline (on timolol alone) and after 4 and 12 weeks' treatment was 24*8 (3.6), 16-8 (4.3), and 15*7 (2.4) mm Hg respectively with once daily application of latanoprost and 24-9 (2.9), 18*1 (3.0), and 18-0 (3.6) mm Hg respectively with latanoprost twice daily. No clinically significant side effects were observed during treatment. Latanoprost causes a marked and sustained IOP reduction in eyes which are also being treated with timolol. Latanoprost given once daily is at least as effective and probably superior to a twice daily dose regimen (BrJ Ophthalmol 1995; 79: 12-16) Several previous studies have demonstrated that the phenyl substituted prostaglandin F2a analogue, 13,14-dihydro-17-phenyl-18, 19, 20-trinor-prostaglandin F2a-isopropylester (latanoprost, PhXA41) and its epimeric mixture PhXA34 reduce significantly the intraocular pressure (IOP) in normal, ocular hypertensive, or glaucomatous eyes."18 The present study was undertaken to obtain more information on dose regimen, long term effect, and additivity to a 13 adrenergic antagonist, timolol.Latanoprost has a long duration of effect on IOP, but whether it should be administered once of twice daily is unclear. In two dose finding studies with the epimeric mixture PhXA34 a duration ofat least 24 hours was observed but the effect 24 hours after the dose was less pronounced than that seen at 12 hours after the dose.' 2 Such an attenuation of the effect was not observed in a study on hospitalised patients treated with latanoprost,7 and in one dose regimen study administration of 0-006% latanoprost once daily was at least as effective as twice daily.4In a first dose finding study with twice daily administrations of latanoprost, ocular hypertensive eyes were treated for 4 weeks.5 There was no significant difference between the three concentrations of latanoprost eye drops used; 0 0035%, 0 006%, and 0-0115%, and all were significantly better than placebo. The initial response, on the second day of treatment, was good with a 31-38% reduction of the IOP, but after 1 week of treatment there was some diminution of effect and after 4 weeks the IOP reduction was between 19 and 22% for the three concentrations of latanoprost used. A partial diminution in the IOP effect was also observed by Camras et al after 5 days of treatment t...