Our overall objective is to identify and understand the factors which control the balance of energy derived from endogenous carbohydrate (CHO) and lipid utilization during sustained, submaximal exercise. The theoretical basis of our approach is the "crossover" concept which we develop fully in our text. Simply put, we believe that during rest and mild to moderate intensity exercise, lipids provide the greatest proportion of energy for exercise. However, as the exercise increases from moderate to hard to maximal, the balance of substrate utilization switches, or 'crosses over' from lipid to carbohydrate. The "Crossover Point" is identified as the power output at which carbohydrate-derived fuels predominate over lipids as energy sources with further increases in power eliciting proportional increments in carbohydrate utilization and decrements in lipid utilization. We further believe that while prior exercise (endurance training) enhances the ability to utilize lipids during mild to moderate intensity exercise, crossover to carbohydrate dependence inevitably occurs in the transition from moderate intensity to hard exercise, crossover to carbohydrate dependence inevitably occurs in the transition from moderate intensity to hard exercise, even in the trained state. In pursuit of our overall objective, we propose to explore five specific aims. These are to: (1) describe the effects of exercise intensity on the balance of energy derived from glucose and free fatty acid (FFA) utilization, (2) described the effects of endurance training on this balance, (3) explore the role of the sympathetic nervous system (SNS), specifically epinephrine, in controlling this balance during exercise, (4) evaluate the role of lactate as a metabolic intermediate, and (5) evaluate the possibility that women may differ from men in their metabolic response to exercise and exercise training. To address these aims, we propose to study men and women at rest and during exercises of give absolute and relative intensities, both before and after long-term training. On men, we plan to also to utilize short- term endurance training, as well as beta-adrenergic blockade in an attempt to dissect sympathetic from other training-induced adaptations on the balance of substrate supply during exercise. Techniques of indirect calorimetry, primed-continuous stable isotope infusion, muscle biopsies and measurements of leg arterial-venous difference [(a-v)] and blood flow as well as response of glucoregulatory hormones will be used to address the above indicated specific aims.