Background: The Ocular Hypertension Treatment Study (OHTS) seeks to evaluate the safety and efficacy of topical ocular hypotensive medication in preventing or delaying the onset of visual field loss and/or optic nerve damage in subjects with ocular hypertension at moderate risk for developing primary open angle glaucoma. Objective: To describe the study protocol, the questions to be answered, and the baseline characteristics of the subjects. Design: Multicenter randomized clinical trial with 2 groups: topical ocular hypotensive medication and close observation. Setting: Subjects were enrolled and evaluated at 22 participating clinical centers. Visual fields and stereoscopic optic disc photographs were read in masked fashion. Methods: We determined eligibility from a comprehensive eye examination, medical and ocular history, visual field testing, and stereoscopic optic disc photography. Results: We describe the baseline characteristics of 1637 subjects randomized between February 28, 1994, and October 31, 1996. The mean age was 55 years; 56.9% of the subjects were women; and 25% were African American. The baseline intraocular pressure was 24.9 ± 2.7 mm Hg (mean ± SD). Systemic diseases and conditions reported by subjects included previous use of medication for ocular hypertension, 37%; systemic hypertension, 38%; cardiovascular disease, 6%; diabetes mellitus, 12%; and family history of glaucoma, 44%. The mean horizontal cup-disc ratio by contour estimated from stereophotography was 0.36 ± 0.18. Qualifying Humphrey 30-2 visual fields had to be normal and reliable for entry into the study. Health-related quality of life (36-item short form health survey) scores in the OHTS sample were better than the age- and sex-matched population norms. African American subjects had larger baseline cup-disc ratios and higher reported rates of elevated blood pressure and diabetes than the rest of the subjects. Conclusions: The intraocular pressure among enrolled subjects was sufficiently high to provide an adequate test of the potential benefit of ocular hypotensive medication in preventing or delaying glaucomatous damage. The large number of African American subjects enrolled should provide a good estimate of the African American response to topical medication.