Previous studies have shown that anterior hypothalamic deafferentation in rats completely suppresses the increase in plasma free fatty acid (FFA), but not the hyperglycemia induced by administration of 2-deoxyglucose, suggesting a specific central regulation of FFA mobilization. The physiological importance of this finding was further investigated by examining in deafferented rats the response to several stimuli that modify the rate of lipomobilization in normal rats. The results show that the hypothalamic lesion interferes with FFA mobilization mainly when increased sympathetic activity is required: during cold exposure or forced muscular activity, and after insulin-induced hypoglycemia or a relatively long period of fasting. Changes in blood sugar responses, when observed, could be interpreted as secondary to an initial block in FFA mobilization. The data support our hypothesis that there are areas in the central nervous system sensitive to glycopenia and activated in situations requiring rapid mobilization of metabolic reserves that can specifically influence FFA mobilization through an activation of the sympathetic fibers of adipose tissue.