Experimentally induced ischemia of the endothelial cells surrounding the aqueous drainage sites led to a rise in intraocular pressure (IOP) in monkey and pigeon eyes. Clinical conditions associated with a rise in IOP in human eyes, e.g. peripheral retinal detachments, subluxated lenses, and occlusion of the internal carotid artery, can result in ischemia of the endothelial cells lining Schlemm’s canal. These findings led to the hypothesis that ischemia of the endothelial cells of Schlemm’s canal induces hypertension in human eyes. Thus, the ischemia hypothesis should be considered in discussions of the etiology of age-related open-angle glaucoma.