In the optic nerve head, the optic nerve fibers are represented by the neuroretinal rim. The rim area showing a high interindividual variability is positively correlated with the optic disc size. This study was performed to address the question of whether, in addition to having a larger neuroretinal rim, eyes with large optic discs also have a higher count of optic nerve fibers compared to eyes with small optic nerve heads. Histologic semithin sections of 72 optic nerves of 56 cornea donors were histomorphometrically evaluated using a computerized image analyzer. The optic nerve fiber count increased significantly (P = 0.01) with enlarging optic disc size. The nerve fiber count was positively correlated with the retrobulbar optic nerve cross section area. It decreased with advancing age, with a mean annual loss of about 4,000 fibers. The nerve fiber density per disc area decreased with increasing optic disc area. Mean and median of the minimal nerve fiber diameter was larger in older subjects. The results may indicate that the optic nerve fiber count, and the anatomic reserve capacity in progressive optic neuropathies, are higher in eyes with large optic discs than in eyes with small optic nerve heads. The optic nerve fiber population decreased with advancing age. This is important for progression, pseudoprogression, and prognosis of optic neuropathies. Optic nerve fiber crowding is more marked in eyes with small optic discs than in eyes with large optic nerve heads. The age-related loss of predominantly small optic nerve fibers can potentiate the optic nerve atrophy in glaucoma and Alzheimer's disease, with both damaging preferentially large axons.