We conducted a randomized, double-masked, long-term clinical trial to determine whether topical timolol therapy was effective in delaying or preventing the onset of glaucomatous damage in moderate-risk ocular hypertensive subjects. In 62 patients, one eye was chosen randomly to receive timolol therapy twice daily while the fellow eye received placebo. During the course of the study, the mean +/- SD difference in intraocular pressure between the timolol-treated and the placebo-treated eyes was 2.3 +/- 2.6 mm Hg. Reproducible visual field loss developed in 4 timolol-treated eyes and 10 placebo-treated eyes. Progressive optic disc cupping was noted in 4 timolol-treated and 8 placebo-treated eyes. Using a computerized image analysis system, the mean +/- SD increase in optic disc pallor during the course of the study was 0.86% +/- 2.4% in the timolol-treated eyes as opposed to 1.80% +/- 3.6% in the placebo-treated eyes. This study provides evidence that lowering intraocular pressure by medical treatment reduces the incidence of glaucomatous damage in ocular-hypertensive individuals.