The possibility of eliciting changes in the activity of lipomobilizing centers in the rat central nervous system was investigated by injecting glucose or substances that affect glucose metabolism directly into the cerebrospinal fluid of conscious, unrestrained rats. Intracerebroventricular administration of minute amounts of 2-deoxyglucose to fed rats induced a rapid increase in the concentration of plasma free fatty acids (FFA) without affecting plasma insulin levels. Furthermore, small amounts of either glucose or insulin injected intraventricularly reduced the increased plasma FFA levels of normal fasted rats without affecting the glycemia or plasma insulin levels in these animals. In diabetic rats, the increased levels of plasma FFA were not affected by intraventricular administration of glucose, but clearly decreased after intraventricular insulin. The results suggest that the lipomobilizing centers are insulin sensitive and that their activity is modulated by the rate of glucose uptake, rather than by external hexose concentration. The data are also consistent with our previous hypothesis of a direct control of the sympathetic tonus of adipose tissue by these centers.