The purpose of this study is to determine whether dystrophin-deficient mdx mice are more susceptible to muscle injury and functional impairment than normal C57 mice when allowed to exercise voluntarily on mouse wheels. The mdx mice were significantly impaired when compared to controls as shown by functional, contractile and morphometric responses. The distance young mdx mice ran was 67-78% of young C57 mice, while adult mdx mice ran 31-48% of adult controls. After exercise the slow, oxidative soleus of young and adult mdx mice exhibited hypertrophy with no changes in strength or fatiguability, while the young C57 mice increased strength and the adults became less fatiguable. In the adult mdx mice the fast EDL, which is primarily glycolytic, exhibits slight hypertrophy with a loss of strength, while the young exhibit no changes. These results indicate that the mdx mouse adapts differently than the C57 mouse to even moderate exercise.