Leigh syndrome (LS) is the clinical prototype of a genetically-determined mitochondrial encephalopathy. Twenty-two of 34 patients with LS had evidence of a movement disorder (MD). Dystonia, the most common MD, was present in 19 cases, rigidity in 4, tremor in 2, chorea in 2, hypokinesia in 2, myoclonus in 1, and tics in 1. Dystonia was most commonly multifocal at onset and showed progression in six patients. In half of the cases an enzymatic defect was detected, most commonly cytochrome C oxidase. The neuroradiologic findings showed prominent basal ganglia lesions in 20/21 patients. Putamen, caudate, substantia nigra and globus pallidus were involved in this order of frequency. This experience was reflected in a literature review encompassing 284 cases of LS. However, only 26.4% had MD. Eleven patients, including one of our cases, presented as the primary torsion dystonia phenotype. There are clinical and pathological similarities between LS and other metabolic diseases affecting the central nervous system. The enhanced vulnerability of the nervous system to metabolic stress and the resemblance in the distribution of the pathology of these diverse conditions suggests a common pathogenetic mechanism. An excitotoxin-mediated mechanism is favored, one which might account for the frequent involvement of the basal ganglia in LS.