Damage to the optic nerve resulting from severe acute glaucoma was studied experimentally in the owl monkey (Aotus trivirgatus). Soon after the onset of glaucoma a widespread marked reduction in blood flow was evident in the optic nerve as well as in the ocular tissues. During the first 4 days there was progressive hydropic degeneration of the nerve head beginning in the vicinity of the lamina cribosa, but extending back into the nerve, mainly in the axial zone. Within 4 to 7 days extensive areas of cavernous degeneration were observed posterior to the lamina, extending back 3 to 6 mm. The nerve head appeared congested and edematous during the first week. Atrophy and early cupping became apparent after 1 week and definite cupping after 2 to 3 weeks. While the areas of cavernous degeneration were rich in acid mucopolysaccharide sensitive to hyaluronidase and typically free of microglial and astrocytic reaction during the first week, after 2 to 4 weeks the cellular response produced a picture resembling infarction. It was concluded that cavernous degeneration of the optic nerve is a peculiar form of ischemic necrosis developing as a consequence of severe acute glaucoma and that the hyaluronic acid, probably forced into the optic nerve from the vitreous, may be one of several factors responsible for the unusual histopathologic picture that characterizes this form of infarction.