In muscle, the neural cell adhesion molecule (NCAM) is known to be expressed in denervated and regenerating fibers. Our present study, performed with immunohistochemical detection procedures, attempts to demonstrate the expression of NCAM in mitochondrial myopathy. Biopsy specimens from 29 patients were investigated. The following conditions were represented: nonweak control subjects (8 cases), chronic progressive external ophthalmoplegia (7 cases), Kearns-Sayre syndrome (5 cases), unclassified mitochondrial myopathy (2 cases), idiopathic polymyositis (7 cases). We demonstrate the expression of NCAM in mitochondrial myopathy. But NCAM is expressed in ragged-red fibers both in mitochondrial and idiopathic inflammatory myopathy. Furthermore, NCAM-immunoreactive fibers are more abundant than ragged-red and cytochrome-c-deficient fibers. Thus, we conclude that NCAM expression precedes histochemical and enzyme-histochemical demonstrable mitochondrial abnormalities. NCAM expression may reflect compensatory regenerating tendency of ragged-red fibers. Vimentin expression in mitochondrial myopathy favors this view. Probably, NCAM plays a role in the enrichment of abnormal mitochondria as a compensatory process for the biochemical deficit. The expression of NCAM in mitochondrial myopathies suggests that NCAM is related to the pathophysiology of these diseases and can be a helpful clue in the diagnosis of mitochondrial myopathy. But NCAM expression is not a specific phenomenon in mitochondrial myopathy, because in secondary mitochondrial changes like in idiopathic polymyositis NCAM expression is observed, too.