Mice that lack both the transcription factor MyoD and dystrophin display a more pronounced myopathic phenotype when compared with mdx mice. No data on skeletal muscle function and the impact of exercise training are available. Six-month-old wild-type, mdx, myoD(-/-), mdx:myoD(+/-), and mdx:myoD(-/-) mice were randomly assigned to either 4 weeks of voluntary running or sedentary behavior. The mdx:myoD(-/-) mice were not able to exercise at all and were kept sedentary. The soleus muscle of sedentary 7-month-old mdx:myoD(-/-) mice showed a significantly lower force development compared with all other mice. Voluntary running beginning at the age of 6 months led to lower force development of soleus muscle in the mdx animals. mdx:myoD(-/-) is not a suitable model to study exercise-induced effects on dystrophic muscles. Voluntary exercise in adult mdx mice seems to have detrimental effects on the function of soleus muscle.