The presence of FFA-mobilizing areas in the rabbit central nervous system was investigated by injecting minute amounts of 2-deoxyglucose, glucose or insulin directly into the cerebrospinal fluid of conscious, unrestrained rabbits. Intracerebroventricular administration of minute amounts (10 mg) of deoxyglucose to fed rabbits produced a rapid increase in the concentration of plasma free fatty acids (FFA) and a slower increase in plasma glucose. Conversely, small amounts of insulin (50 μU) or glucose (2.5 mg) intraventricularly reduced the elevated plasma FFA of normal fasted rabbits without affecting plasma levels of glucose or insulin. The elevated levels of plasma FFA of diabetic rabbits were not affected by glucose administration, but clearly decreased after intraventricular insulin. Adrenodemedullation suppressed the hyperglycemia but not the plasma FFA increase induced by intraventricular 2-deoxyglucose. The data suggest that insulin-sensitive centers in the rabbit central nervous system participate in the control of FFA mobilization during fasting by modulating the lipolytic sympathetic tonus of adipose tissue, and that the activity of these centers is regulated by their rate of glucose utilization.