Formerly or reduced-obsese (RO) subjects exhibit diminished systemic energy requirements for weight maintenance. Based on studies in animals and humans, there is reason to believe that the autonomic nervous system (ANS) plays an important role in coordinate regulation of energy metabolism and may be altered in the RO state. We have, therefore, investigated aspects of autonomic physiology in obese (OB), RO, and never obese (NO) subjects subjected to insulin-mediated hypoglycemia and incremental intravenous infusions of epinephrine. Total catecholamine secretion during insulin-induced hypoglycemia was significantly lower in the RO. The RO showed increased sensitivity to in vivo lipolytic and cardiovascular effects of endogenous and infused catecholamines. In these studies, OB subjects responded more like the NO subjects than did the RO. The RO display characteristic changes in autonomic status that may play a role in their enhanced energy efficiency.