The 55-64 year-old age group is the fastest growing sector of the labor force in the United States, and approximately 20% of the labor force will be over 55 years oldby 2006. However, the effects of aging on the susceptibility to musculo-skeletal injury following chronic, repetitive loading have not been comprehensively investigated. To investigate the skeletal muscle response to a chronic administration of stretch-shortening cycles (SSCs) in young and old rats. Training was performed on the dorsi-flexor muslces of the left limb in young (age = 12 wks) and old (age = 30 m) Fischer 344 x Brown Norway rats in vivo. The training protocol consisted of 8 sets of 10 SSCs administered 3 times/week over 4.5 weeks. The SSCs were conducted at a velocity of 60/s throughout a 90-140 degree range of motion. The right limb acted as the intra-animal control. Twenty four hours following the final exposure rats were weighed, anesthetized and exsanguinated. The left and right tibialois anterior muscle (LTA, RTA) was excised, weighed, sectioned, quick-frozen, and stored at -80C. Transverse sections (12 um) were cut, mounted on pre-coated microscope slides, and stained using a routine procedure with Harris Hematoxylin and Eosin. Tissue sections were evaluated on a Leica DMLB microscope. Stereology was used to quantify the degree of inflammation and myofiber degeneration in muscle from each group and modifications to the interstitial space. The LTA muscle wet weight was significantly greater than the RTA muscle weight in young rats (p<0.001). In contrast, no differences were observed between the old LTA and old TRA muscle weight. Furthermore, a significant increase was observed in the young LTA compared with the old LTA (p<0.001). Stereological analyses revealed no degenerative myofibers in young or old animals. However, there was a significant main efect for age of the volume density of cellular interstitium (CI) (p=0.02). Further analysis indicated that the volume density of CI was greater in the LTA compared to the RTA (p=0.05) in old rats and when compared with the LTA in young rats (p=0.01). Young animals adapted to 4.5 weeks of SSC-training by significantly increasing muscle mass, whereas old animals did not. In addition, muscles from the old animals exhibited an increased cellular interstitial response (not found in the young animals) in the absence of myofiber degeneration and edema.