We studied muscle biopsies from 36 Becker muscular dystrophy patients, and correlated dystrophin negative fibers with regenerating and degenerating myofibers. Dystrophin immunohistochemistry was used to identify dystrophin-negative and dystrophin-positive fibers. Immunohistochemical staining for fetal myosin and acid ATPase identified regenerating fibers, and calcium glioxalate and beta-spectrin staining identified necrotic fibers. All Becker biopsies contained detectable dystrophin in the majority of muscle fibers. 13 cases (36%) showed no dystrophin negative fibers, 9 cases (25%) showed a generalized, markedly decreased immunostaining pattern, and 14 cases (39%) showed a subset of dystrophin negative fibers (0.3-8% of total). Most dystrophin-negative fibers in Becker muscle were judged to be in the process of regeneration, and not in degeneration. No correlation was observed between the age of the patients and number of dystrophin negative fibers. We conclude that the absence of dystrophin and spectrin labeling in some BMD myofibers is associated with regeneration, probably due to incomplete expression of dystrophin secondary to myofibers immaturity. Our results might be explained by a developmental delayed expression of these two proteins, or by abnormal assembling in membrane's components during regeneration in dystrophy. Furthermore, our results rationalize the recently reported finding of some dystrophin-negative fibers in polymyositis.