This study was undertaken to measure number, diameter and distribution of nerve fibers in normal human optic nerves. Twenty-two optic nerves of 19 subjects aged between 20 and 75 years were histomorphometrically examined using semithin sections obtained in a distance of 2 to 5 mm behind the globe. The mean nerve fiber count was 1,159,000 +/- 196,000 with a minimum of 816,000 and a maximum of 1,502,000. The significant (P = 0.025) loss per year of age was approximately 5426 nerve fibers. For eight subjects the nerve fiber count was independent of the size and form of the optic disc. The mean minimal nerve fiber diameter averaged 1.00 +/- 0.06 micron (range: 0.1-8.3 microns). It was significantly smaller in the temporal and inner region of the optic nerve than in the nasal and outer area, respectively. Correspondingly, nerve fiber count per area was significantly higher in the temporal and inner parts of the optic nerve than in the nasal and outer parts, respectively. Statistically different size classes could not be detected. The optic nerve cross-section area excluding the leptomeninges (mean 8.09 +/- 1.38 mm2) increased significantly with the nerve fiber count. The marked interindividual variability of the nerve fiber count may influence interindividual comparisons of psychophysical examinations. It can indicate an interindividually different anatomic "reserve capacity" in the course of optic nerve diseases. The age-dependent nerve fiber loss, among other factors, may partially explain the decreased visual performance of older subjects. It should be considered in progression and "pseudoprogression" of optic nerve diseases like glaucoma. The intraindividually high variability of the nerve fiber size may correspond to different retinal ganglion cell populations.