The aim of this study was to examine the ultrastructure of axonal cytoskeletons in guinea pig optic nerve damage induced by acutely elevated intraocular pressure (IOP) employing the quick-freezing and deep-etching method. An IOP of 60 mm Hg was maintained for 4 h. The unmyelinated axoplasm of the optic nerve at the normal IOP was filled with longitudinally oriented neurofilaments and bundled microtubules, which were cross-linked by numerous cross-bridges. Membranous organdies, such as mitochondria and vesicles, were scattered in the axoplasm. These organelles were similarly interconnected with microtubules or neurofilaments by the cross-bridges. The unmyelinated axoplasm of the optic nerve following acutely elevated IOP was shown to include intra-axonal collections of various membranous organelles and reduction of microtubules and neurofilaments. The cross-bridges linking microtubules, neurofilaments and membranous organelles in such axoplasm appeared to be dramatically reduced in number. Thus, it is suggested that the ultrastructural changes of axonal cytoskeletons in some optic nerves following elevated IOP might include the reduction of microtubules, neurofilaments and their associated cross-bridges.