We conducted a six-month prospective, double-masked randomized trial comparing betaxolol with timolol at 0.25% and 0.5% concentrations in the treatment of primary open-angle glaucoma in 38 patients. To qualify, patients had to demonstrate an average intraocular pressure in at least one eye of greater than or equal to 26 mm Hg without treatment. The median intraocular pressure was consistently lower in the timolol group than in the betaxolol group (after four weeks of therapy, it was 20.2 mm Hg for timolol vs 22.5 mm Hg for betaxolol; P less than .04). Adjunctive therapy was required in eight patients in the betaxolol group compared to one in the timolol group (P less than .05). Betaxolol appears to be a clinically effective and safe agent in the treatment of open-angle glaucoma. However, the magnitude of the decrease in intraocular pressure with it may not be as great as that with timolol and there may be a greater need for adjunctive therapy with it than with timolol.