The current view indicates that after eccentric exercise myofibers are mechanically damaged and therefore an inflammatory and necrotic process occurs. In the present paper we examine the possibility that apoptosis plays a role in normal and dystrophin-deficient muscles after running. We analysed for apoptosis normal and dystrophin-deficient mouse muscles after a night of spontaneous wheel-running followed by two days of rest. Terminal deoxynucleotidyl transferase-mediated end-labeling of DNA in nuclei in tissue sections and gel electrophoresis of extracted DNA showed the presence of fragmented DNA. Furthermore, ubiquitin, a protein whose appearance is related to apoptosis, increased in muscles of both dystrophic and normal runner mice. The present findings which confirm that DNA damage is absent in muscles of sedentary mice but present in muscles of runner mice offer a new hypothesis on early events of muscle damage.