In order to study whether myofiber size is an important determinant of the severity of dystrophic injury, mdx and control mice were treated with an anabolic steroid, nandrolone decanoate, for 3 weeks. Treatment resulted in a population of significantly smaller fibers in both strains, and was accompanied by an increase in the proportionate area or the number of foci of dystrophic injury in mdx soleus (slow-twitch) or tibialis anterior plus extensor digitorum longus (fast-twitch) muscles, respectively. As well, serum creatine kinase activity was increased in steroid-treated mdx mice. Fiber centronucleation, an index of accumulated injury and repair, in steroid-treated mdx soleus was doubled compared to that observed in soleus muscles from untreated mdx mice. There was no change in the distribution of immunoreactive basic fibroblast growth factor, important in muscle cell proliferation, with the increased damage from treatment. However, presumptive muscle precursor cells (identified by immunoperoxidase histochemistry for neural cell adhesion molecule), appeared to be more abundant in foci of very recent fiber damage in muscles from steroid-treated than untreated mdx mice. Results show that mdx dystrophy is worsened by anabolic steroid treatment, possibly by altered influences on muscle use patterns and muscle precursor fusion, and is not accompanied by an increase in fiber size.