Previous studies suggest that Leber's hereditary optic neuropathy (LHON) may be a systemic disorder with manifestations in organs other than the optic nerves. To evaluate nervous system involvement 38 men and eight women with LHON were re-examined. The patients were divided into three groups according to mtDNA analysis--namely, patients with the 11778 or with the 3460 mutation and patients without these primary mutations. Fifty nine per cent of patients had neurological abnormalities but there was no significant difference between the three groups. Movement disorders were the most common finding; nine patients had constant postural tremor, one chronic motor tic disorder, and one parkinsonism with dystonia. Four patients had peripheral neuropathy with no other evident cause. Two patients had a multiple sclerosis-like syndrome; in both patients MRI showed changes in the periventricular white matter. Thoracic kyphosis occurred in seven patients, five of whom had the 3460 mutation. In one patient the 3460 mutation was associated with involvement of the brain stem. It is suggested that various movement disorders, multiple sclerosis-like illness, and deformities of the vertebral column may associate pathogenetically with LHON.