The role of adrenoceptors in the hypothalamus and the peripheral sympathetic nervous system in the regulation of sympathoadrenal activity and glucose and FFA mobilization was investigated in exercising rats. Apparent close relations within the two parts of the sympathoadrenal system and between factors that regulate glucose and FFA mobilization during exercise were completely disrupted by local hypothalamic infusions of adrenoceptor antagonists or anesthetic drugs. The experiments actually identified specific areas in the hypothalamus that integrate the information regarding the substrate levels in the blood with the “central command” from higher centers in the brain. Furthermore, the results of experiments with exercising intact and adrenodemedullated (Adm) rats, with and without administration of selective adrenoceptor agonists and antagonists, suggest that the activity of the sympathetic nervous system is also regulated at the level of the peripheral sympathetic nerve endings. In particular, presynaptic adrenergic regulatory mechanisms can markedly influence the outflow of NE from the sympathetic nerve endings. In conclusion, the data show that an organ-specific organization of sympathetic output during exercise may take place at different levels within the sympathetic nervous system.