The purpose of the present study was to compare the myogenic response of hindlimb muscles in young (14-20 wk of age) and old (>120 wk of age) rats with a single exhaustive bout of heavy resistance weight lifting. [(3)H]thymidine and [(14)C]leucine labeling were monitored for up to 2 wk after the exercise bout to estimate serial changes in mitotic activity and the level of amino acid uptake and myosin synthesis. Histological, histochemical, and immunohistochemical [anti-5-bromo-2'-deoxyuridine and myogenic determination genes (MyoD)] analyses of whole muscles and analysis of muscle-specific gene expression (MyoD) using Western blotting and RT-PCR were performed. Old rats showed significant muscle atrophy and a lower exercise capacity than young rats. Exercise-induced muscle damage, as assessed in histological sections, and increases in serum creatine kinase activity were evident in both young and old exercised groups. Mitotic activity was increased in young, but not old, rats 2 days after exercise. There was a biphasic increase in [(14)C]leucine uptake during the 14 days postexercise (peaks at 1-4 and 10 days) in young rats: only the first peak was observed in old rats. There was a lower uptake of [(14)C]leucine in the myosin fraction and an impaired expression of MyoD at the protein (immunohistochemistry and Western blotting) and mRNA (RT-PCR) levels in old rats throughout the postexercise period. These results demonstrate a reduced reparative capability of muscle in response to a single bout of exercise in old compared with young rats.