• Prostaglandin F2α-isoprophylester (PGF2α-IE) (0.5 μg) or placebo was added twice daily for 1 week to one eye in each of 30 patients with open angle glaucoma not adequately controlled with timolol treatment. Compared with placebo, PGF2α-IE reduced the intraocular pressure of these timolol-treated eyes significantly. The absolute difference in mean change between PGF2α-IE and placebo groups was 4.5 mm Hg with a 95% confidence interval of 3.1 to 6.6 mm Hg, corresponding to a mean reduction of initial intraocular pressure of 17.4% in eyes treated with PGF2α-IE. Conjunctival or episcleral hyperemia was seen in all eyes treated with PGF2α-IE for up to 4 hours but not in eyes treated with timolol and placebo, and aqueous flare was not observed in any eye. Thirteen of 15 patients treated with PGF2α-IE, compared with only 3 of 15 who received placebo, reported mild to moderate subjective discomfort in the treated eye in the form of a foreign-body sensation that lasted for up to 2 hours. These results demonstrate that PGF2α-IE, in a dose that has previously been shown to reduce intraocular pressure in normotensive volunteers or in patients with glaucoma who are taking no other medications, also significantly reduces the intraocular pressure of patients with glaucoma whose pressures are not adequately controlled on a twicedaily regimen of timolol.