A feedback system for the regulation of food intake and body weight, consisting of two elements is proposed. One is related to the quantity and quality of the food ingested. It consists of neural afferents, psychosocial conditioning factors, and peptide signals from the gastrointestinal tract released by specific nutrient intake. The other is also sensitive to nutrient intake, but importantly modulated by relative adiposity. We present evidence to suggest that insulin serves as the key feedback signal to the central nervous system to serve this second function (body adiposity signal). Insulin has been found in cerebrospinal fluid where it concentration is increased by systemic infusions of glucose or insulin and is proportional to its concentration in plasma. When insulin (10 and 10 micro U/kg/day) is infused into the lateral cerebral ventricles of free feeding baboons a dose dependent suppression of food intake and body weight is found. Intravenous infusion of 25% and 50% of total calories as glucose elevates endogenous insulin concentrations and suppresses food intake. These findings suggest that the amount of insulin secreted per day and more modulates food intake to maintain a constant body weight.