Muscle biopsy specimens of two patients with fatal reducing body myopathy showed few necrotic or regenerating fibers. On the other hand, enlarged densely stained myonuclei, in addition to the presence of many reducing bodies, were striking on light microscopy, and chromatin condensation was seen on electron microscopy. To confirm the involvement of apoptosis, we performed the TUNEL method at the electron microscopic level on muscles of the two patients and five age-matched controls. The density of DNA fragments in myonuclei showing chromatin condensation was significantly higher in reducing body myopathy compared to that in control muscles. In addition, the myonuclei surrounded by many reducing bodies tended to show more intense chromatin condensation and a higher density of DNA fragments than those distant from the reducing bodies. These results suggest that apoptosis takes part in muscle fiber degeneration in fatal reducing body myopathy, although the precise relationship between reducing bodies and apoptosis is uncertain.