Detailed testing of higher cerebral function was performed in 36 patients with mitochondrial myopathies and encephalomyopathies. Fourteen of these patients were thought to be cognitively impaired on clinical grounds. The assessments included tests of general intellectual ability and focal tests of memory, language, and perception. Twenty-one (58%) of the 36 patients who were tested had evidence of general intellectual deterioration, with focal cognitive deficits of variable degree. Of the remaining 15 patients in whom there was no evidence of general intellectual decline, five displayed focal cognitive deficits. In only 10 patients was there evidence of cerebral dysfunction. The range and extent of cognitive deficits in mitochondrial myopathies are greater than predicted by their clinical presentations.