We performed a 5-year clinical and electrophysiologic follow-up study on two sibling cases with myoclonus epilepsy with ragged-red fibers. Both had myoclonus, intention tremor, slight muscle weakness, slight mental disturbance, hearing impairment, and optic atrophy. Neither had epileptic attacks or truncal or gait ataxia. Biochemical activity of cytochrome c oxidase was at the lower limit of the normal range of values, and an adenine to guanine transition mutation at nucleotide 8344 in the transfer RNA specific for lysine of mitochondrial DNA was detected in both cases. The electroencephalograms showed slowing of basic patterns, diffuse spike-and-wave complexes, occipital dominant wave-and-spike phantoms, 6- and 14-Hz positive spikes, and photosensitivity. No definite deterioration of basic patterns was seen, and diffuse spike-and-wave complexes and photosensitivity gradually disappeared during the slowly progressive clinical course. P2 latencies of pattern-reversal visual evoked potentials throughout the clinical course and III through V interpeak latencies of auditory brainstem responses at follow-up were prolonged without giant sensory evoked potentials in both cases.