Leber's hereditary optic neuropathy is associated with three different point mutations of mitochondrial DNA that appear to be pathogenetic for the disease. These mutations affect nucleotide positions 3460, 11,778, and 15,257. We reviewed the clinical characteristics of 12 visually symptomatic patients from nine families with the 3460 mutation and compared them with previously published characteristics of symptomatic patients with the 11,778 mutation. The patients with the 3460 mutation were similar to the patients with the 11,778 mutation in most clinical parameters. However, the patients with the 3460 mutation had a higher incidence of visual recovery (20% vs 4%, P = .001), a higher percentage of pedigrees with more than one affected family member (78% vs 43%, P = .011), and a greater frequency of tobacco and alcohol abuse. The difference in visual prognosis between these two mutations and the need for modification of possible risk factors provide added significance to genetic testing for Leber's hereditary optic neuropathy.