Previous studies have provided some evidence to suggest that the different types of myosin present in skeletal muscle can be modified enzymatically by repeated bouts of physical activity. To date, however, no studies have been designed to adequately test the hypothesis that the myosin isozyme pattern of a given muscle can be regulated in accordance with the functional demands of gaiting speed and of force imposed on it during repeated conventional exercise (running). We propose to test this hypothesis by using a normal animal modeland an overload model in which the medial gastrocnemius and rectus femoris muscles are surgically isolated to be primarily responsible for muscle activity involving the hindlimb musculature. This intervention will limit the total number of fast-twitcha nd slow-twitch motor units participating in locomotion, thereby forcing any potential adaptation to become highly focused. After 8 weeks of surgical induced overload, the overloaded animals, along with normal controls, will be subjected to identicle chronic exercise programs in which the variables of (1) speed and (2) incline or weight addition to animals will be selectively changed. some animals will be instrumented for electromyographic recordings to monitor the relative activation of the muscles during locomotion. At the termination of a given exercise program, the nuscles will be analyzed for: (1) contractile and fatigue properties; (2) Ca++ regulated myofibril ATPase; (3) histochemistry to assess fiber-typing; (4) citrate synthase activity; and (5) myosin analyses consisting of ATPase (including alkaline and acid inactivation), light chain electrophoretic patterns, and native myosin electrophoresis to identify specific fast and slow isozymes. With this combination of exercise models, we should be able to assess how physiological stimuli alter the genetic expression of skeletal muscle in terms of contractile function.