The extent and contribution of myosin heavy chain plasticity in the adaptive response following glutathione modulation and repetitive mechanical loading is not known. PURPOSE: The purpose of this research was to identify the influence dietary supplementation with a glutathione antagonist (L-Buthionine Sulfoximine (BSO)) has on the adaptability of skeletal muscle during chronic high-intensity mechanical loading via stretch-shortening contractions (SSCs) in young and old rats. METHODS: Left dorsiflexor muscles of young (12 weeks, N= 22) and old (30 months, N = 22), vehicle- (VEH) and BSO-treated rats were exposed 3 times per week for 4.5-weeks to a protocol of 80 maximal SSCs per exposure in vivo, while cage, age-matched rats served as controls (CON). Myofiber plasticity was characterized by myosin heavy chain (MHCslow+, MHCfast+, or MHCdev+) response by immunohistochemical analysis, as well as by changes in muscle cross-sectional area distribution following the exposure period. RESULTS: MHCslow+ content was increased in the old rats, irrespective of treatment or exposure. Conversely, MHCfast+ content was increased in the young rats, regardless of treatment of exposure. MHCdev+ content was not changed following chronic SSC loading. Shifts to larger fiber cross-sectional areas were apparent for all SSC-exposed groups. CONCLUSIONS: MHCdev+ is not expressed following chronic SSC exposure, regardless of age, treatment, or exposure. Aging skeletal muscle does retain some capacity for adaptation; however aging apparently diminishes the adaptive response following chronic SSC exposure. Evidently, a population of small myofibers does exist that do not undergo regeneration in aged skeletal muscle, perhaps accounting for the disparity observed between morphological adaptation and functional performance.