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Plasma creatine kinase (CK) activity has often been used as a marker of exercise-induced skeletal muscle damage. While the pattern of muscle damage following eccentric exercise has been established in young adults, there is little data available on eccentric exercise-induced muscle damage in older individuals. The purpose of this study was to compare ultrastructural changes in skeletal muscle following high intensity eccentric exercise of young and older men and to determine whether CK activity is a reliable predictor of muscle damage. Five young (20–30 yr) and five older untrained men (59–63 yr) performed three 15-min bouts of eccentric exercise at 90, 80, and 70% of maximal concentric power output. There was a prolonged increase in CK up to 10 d following exercise that was not significantly different between groups. Light and electron microscopic examination of needle biopsies obtained from the vastus lateralis showed evidence of focal damage in greater than 90% of the post-exercise fibers examined in the older subjects, compared with values ranging from 5 to 50% reported previously in young subjects. Quantitative analysis using light microscopy snowed greater damage in the older subjects than reported previously in young subjects. These data suggest that older adults experience greater muscle damage following eccentric exercise than young subjects, which may be due in part to the smaller muscle mass and lower O2max seen in older men. In addition, there was no relationship between CK activity and the corresponding amount of muscle damage observed in each subject, suggesting that CK activity may be a poor predictor of exercise-induced muscle damage.