A new double mutant mouse strain, gad-mdx, was established. The transmission of mdx and gad genes was monitored by determining their chemical markers, creative kinase activity and phosphoglucomutase-1 isoenzyme, respectively, in blood samples. This new strain was characterized by high creatine kinase activity in the plasma, lack of dystrophin in the muscle, and the presence of axonal swellings in the neural tissue. Although the body weight and the limb muscle size of the mutant mice were significantly lower than those of either gad or mdx mice, the clinical signs were not evident until the animals were 80 days old. After that time, the disease followed the course seen in the gad strain, and muscle weakness was exhibited in the advanced stages. Histologic examination revealed that the prevalence of muscle fiber necrosis, a deleterious consequence of the mdx gene, was significantly lower in the double mutant strain than in the mdx strain. These results supported the idea that small-caliber muscle fibers, which are induced by gad gene expression, are resistant to dystrophic necrosis. We believe that this double mutant strain will be valuable for the analysis of neural influence on diseased muscle fibers, and that it will also provide an opportunity for the testing of new therapeutic strategies for human Duchenne muscular dystrophy.