Histological, histochemical, and morphometric analyses were performed chronologically on muscles from mutant mice with X chromosome-linked muscular dystrophy (mdx), and the findings were compared with those in nondystrophic control animals (C57BL/10ScSn). Massive grouped muscle fiber destruction, followed by complete regeneration, occurred abruptly at 20 days of age. There were no preceding changes in body weight, the number and mean diameter of fibers, and fiber type differentiation before the initial episode of muscle fiber necrosis. Muscle fiber necrosis decreased in intensity after 60 days of age. Even after repeated muscle fiber necrosis and regeneration, the most striking finding was that interstitial fibrosis and adipose tissue replacement were minimal, and there was no apparent fiber loss. Since the necrosis was probably well compensated by the active regenerative process, themdx mice developed no obvious muscle weakness and thus differed from human and other animal muscular dystrophies with the exception of the dystrophic hamster.