The purpose of this study was to determine the extent to which hindlimb muscles of mdx mice adapt to a voluntary endurance type of exercise. mdx and C57BL mice engaged in 8 weeks of wheel running or maintained normal cage activities. Beneficial adaptations that occurred in mdx mice included changes in muscle mass, fiber size, and fiber types based on myosin heavy chain (MHC) isoform expression. These adaptations occurred without increases in fiber central nuclei and embryonic MHC expression. An undesirable outcome, however, was that muscle mitochondrial enzyme activities did not improve with exercise in mdx mice as they did in C57BL mice. Cellular remodeling of dystrophic muscle following exercise has not been studied adequately. In this study we found that some, but not all, of the expected adaptations occurred in mdx mouse muscle. We must better understand these (non)adaptations in order to inform individuals with DMD about the benefits of exercise. Muscle Nerve 38: 1290–1303, 2008