Blink reflex (BR) was studied in 17 patients with histochemically and genetically confirmed mitochondrial myopathy (MM). Fourteen patients had chronic progressive external ophthalmoplegia (CPEO) associated with a mild to moderate craniosomatic myopathy without any symptoms or signs of central nervous system (CNS) involvement, 2 myoclonic epilepsy with ragged red fibers syndrome, and 1 Kearns-Sayre syndrome. The mean latencies of the early (R1) and late (R2) responses were prolonged (P < 0.01 and P < 0.001, respectively), and the corresponding amplitudes decreased (P < 0.001). Increased habituation of the reflex was clearly observed in 10 out of 14 patients tested (71.4%), 9 of whom presented CPEO. These findings suggest that the brain stem reticular network is in a state of basal inhibition which is presumably due to a subclinical impairment of the cerebral cellular metabolism. Multimodal evoked potentials revealed abnormalities suggestive of CNS involvement in 7 out of 17 patients (41.2%), 4 of whom had CPEO. These observations document the validity of BR in detecting clinically silent brain stem impairment in patients with apparently pure MM and provide important clues for a further understanding of the underlying pathophysiology.