It is postulated that age impairs the ability of skeletal muscle to regenerate to mechanical loading due to the occurrence of increased injury. Nevertheless, the mechanism/s accounting for this disparate response with increased age is not fully understood. Experiments using stretch-shortening contractions (SSCs) provide a model to investigate skeletal muscle regeneration in response to strain injury in young and old animals. PURPOSE: To investigate the effect of a graded, injurious SSC exposure in young and old rats. METHODS: Left dorsiflexor muscles (LTA) of young (12 wks; n=5) and old (30 mo; n=5), male F344xBN Hybrid rats were exposed to an increasing number of 0, 30, 80, and 150 injurious SSCs in vivo. The contra-lateral right limb (RTA) served as an intra-animal control. Changes in muscle morphometry were quantified at 3 days post-injury. The left and right tibialis anterior muscles (LTA & RTA) were excised, prepared for histology, and 12 Ám transverse sections were prepared and stained using H&E. Tissue sections were assessed using a standardized, quantitative stereological method. RESULTS: No significant indices of histopathology were revealed in young RTA tissue, whereas old control tissue revealed decreased normal myofibers, increased degenerative myofibers, and increased non-cellular interstitium (indicative of edema; p<0.05). Following SSC-strain injury in young rats, data indicated a decrease in percent tissue fraction of normal myofibers (p<0.05) and an increase in non-cellular interstitium and cellular interstitium (p<0.05) as the number of SSCs were increased to 150 SSCs. However, the percent tissue fraction of degenerative myofibers was increased only following 80 SSCs (p<0.05) and plateaued thereafter in young rats. These findings were not observed in muscles from old rats, and no consistent exposure-response was noted. CONCLUSION: These data indicate that young muscles exposed to increasing grades of injurious SSCs exhibit an exposure-response relationship supported by histopathological findings, while the histopathological findings in muscles from old rats are attenuated. Therefore, given these findings, we suggest that edema, inflammation, and degeneration are fundamentally necessary components preceding competent muscle regeneration that leads to healing.