Axonal degeneration and diminution of the axonal population in the optic nerve have been documented in aging and in various neuro-ophthalmic conditions. We applied morphometric techniques to the postmortem examination of optic nerves obtained from patients with acquired immunodeficiency syndrome. Twelve optic nerves (eight from patients with AIDS and four from age-matched control eyes) were stained with paraphenylenediamine and morphometrically analyzed with a computer-assisted image and measurement system. Degeneration was often severe and was scattered throughout all of the AIDS-affected optic nerves. In the AIDS-affected optic nerves, the mean axonal population was markedly lower than the mean obtained from normal optic nerves (880,000 vs 1,507,000). Despite the approximate 40% loss of axons, mean axonal diameters were not markedly different, suggesting that no particular class of axon was especially susceptible to AIDS-associated degeneration. The extent and pattern of axonal loss in optic nerves of patients with AIDS suggest that the changes may not only be secondary to damage at the retina, but may reflect an AIDS-associated primary optic neuropathy.