OBJECTIVE To compare intraocular pressure (IOP) after adding either latanoprost or pilocarpine to timolol treatment or switching to latanoprost monotherapy in glaucomatous eyes in which IOP was inadequately controlled with timolol. METHODS This 6-month randomized study comprised 148 patients with primary open-angle or pseudoexfoliation glaucoma, which was inadequately controlled with topical beta-adrenergic antagonists. After a 2- to 4-week run-in period with timolol 0.5% twice daily, patients were assigned in randomized fashion to three study groups: one group received add-on therapy of latanoprost 0.005% once daily, the second group received add-on therapy of pilocarpine 2% three times daily, and the third group switched to latanoprost 0.005% once daily. Mean diurnal IOP was measured at baseline and after 3 and 6 months of treatment. RESULTS At 6 months, 128 patients had completed the study. Diurnal IOP was significantly reduced from baseline in all groups. Adding latanoprost to timolol treatment reduced diurnal IOP by 6.1+/-0.3 mmHg (-28%), adding pilocarpine to timolol treatment reduced diurnal IOP by 4.2+/-0.3 mmHg (-19%), and switching from timolol to latanoprost monotherapy reduced diurnal IOP by 5.5+/-0.3 mmHg (-25%). CONCLUSIONS A significantly greater reduction in diurnal IOP was achieved after addition of latanoprost than after addition of pilocarpine in patients in whom IOP was not adequately controlled with timolol alone. Further, the results of this study indicate that a switch to latanoprost monotherapy can be attempted before combination treatment is initiated.