In order to assess the contribution of fundus examination to the differential diagnosis of acuqired optic neuropathy, five ophthalmologists viewed 163 fundus stereophotographs of nine disease entities as "unknowns." Glaucoma, central retinal artery occlusion (CRAO), and ischemic optic neuropathy (ION) were diagnosed by at least one observer with an accuracy above 80%. The remaining conditions (optic neuritis; compressive, traumatic, and hereditary optic neuropathies) were correctly identified with less than 50% accuracy. Retinal arteriolar attenuation and sheathing were most helpful in differentiating CRAO and ION. Although pathologic disc cupping often identified glaucoma, it was also seen in 20% of eyes with optic atrophy not associated with glaucoma. Excavation was more profound in glaucoma than in nonglaucomatous optic atrophy, the latter demonstrating relatively greater neuroretinal rim pallor. In 6% of nonglaucomatous optic atrophy eyes, however, disc cupping was misdiagnosed as "glaucomatous." Only 11% of eyes with previously documented papillitis or ION left clues that allowed observers to identify preexisting disc swelling.