The prevalence of internal nuclei in muscle fibers (centronucleation), which is a reliable cumulative index of all prior muscle fiber necrosis, was measured at different ages in different muscles of mdx mice and was correlated with muscle fiber diameter. The prevalence of centronucleated fibers (as percentage of total number of fibers) rose gradually after age 20 days until it reached a peak level of 80% at age 60 days. No significant centronucleation (or necrosis) was observed in the following circumstances: in 4 different limb muscles before age 15 days, in leg muscles that were denervated by peripheral nerve section or rendered immobile by high thoracic cordotomy at 15 days, or in rotator extraocular muscles throughout the animals' life span. In these situations, muscle fiber diameter remained below approximately 20 micron. The mechanism by which small-diameter fibers are resistant to necrosis in mdx dystrophy is unknown, but a similar situation exists in hamster and Duchenne muscular dystrophy.