Epinephrine (1.25%) was applied topically twice daily to both eyes of 22 patients with glaucoma or ocular hypertension. Half of these patients received topical indomethacin (0.5%) three times daily in one eye; the other half received indomethacin placebo under the same regimen. Blood-aqueous and blood-retinal barrier functions were determined by aqueous and vitreous fluorophotometry before and 1, 2, 3, and 7 months after initiation of treatment. Epinephrine-induced disruption of the blood-aqueous barrier, noted at two months, apparently remained constant until the completion of the study. At months 2, 3, and 7, indomethacin significantly inhibited this disruption. The blood-retinal barrier was unaffected. These results bear on the hypotensive mechanism of topically applied epinephrine.