Many investigators have reported that abnormalities in the retinal nerve fiber layer may be the earliest sign of primary open-angle glaucoma. We attempted to create defects in the retinal nerve fiber layer in experimentally induced glaucoma and to examine their histology. By repeated circumferential argon laser photocoagulation of the trabecular meshwork of normal cynomolgus monkeys, we succeeded in causing a continuous increase in intraocular pressure (IOP). During the course of this experiment, cupping of the optic nerve head, wedge-shaped retinal nerve fiber layer defects, and halo glaucomatosus developed, all of which are defects that are similar to those seen clinically in primary open-angle glaucoma. The IOP required for this fundus change was 25, 35, and 43 mmHg, indicating great individual variation. Histological examination revealed localized degeneration, loss of axon bundles, and diffuse thinning of the nerve fiber layer in the area of these wedge-shaped defects in the retinal nerve fiber layer. These results may indicate that the optic-nerve-damaging mechanism, both localized and generalized, is the same in the cynomolgus monkey and in man.