Control by the central nervous system of neural and humoral thermoregulatory mechanisms was studied in conscious baboons. Local cooling and warming of the anterior hypothalamus respectively stimulated and inhibited the sympathico-adrenomedullary system and the adrenal cortex. These endocrine responses correlated with physical heat gain and heat loss and with thermoregulatory behavior. Evidence of and essential role of the sympathico-adrenomedullary system in thermogenesis was obtained when baboons were treated with a ganglionic blockingagent. Intrahypothalamic infusion of norepinephrine lowered internal temperature as did central warming, suggesting that this monoamine may be a central neurotransmitter triggering heat loss. Systemic and intrahypothalamic infusion of adrenergic blocking agents provided evidence for an adrenergic mechanism mediating reciprocal secretion of growth hormone and insulin.