Thermoregulatory mechanisms are remarkably efficient, ensuring minimal temperature variation within the core of the human body under physiological conditions. Diverse afferent and efferent neural pathways contribute to the monitoring of core and skin temperature, generation of heat, and control of thermal exchange with the external environment. We have investigated the cortical, thalamic, and hypothalamic responses to cooling and warming by using positron-emission tomography activation imaging of subjects clad in a water-perfused suit, which enabled rapid change of their skin-surface temperature. Human brain regions that respond to changes in skin temperature have been identified in the somatosensory cortex, insula, anterior cingulate, thalamus, and hypothalamus, with evidence that the hypothalamic response codes for the direction of temperature change. We conclude that signals from thermosensors in the skin providing crucial afferent information to the brain are integrated with signals from central thermosensors, resulting in thermoregulatory responses that maintain core temperature within a remarkably narrow range.functional neuroimaging ͉ hypothalamus ͉ thermoregulation T he integrity of the human body depends on the maintenance of the internal environment at a relatively constant temperature. Thermoregulatory mechanisms are remarkably efficient, ensuring small temperature tolerances within the core of the body under physiological conditions. Diverse afferent and efferent neural pathways contribute to the monitoring of core and skin temperature, generation of heat, and control of thermal exchange with the external environment. The integration of these processes is a function of the central nervous system within a network that has only been partially described in humans.The reflex regulation of body temperature is usually considered in the context of a traditional feedback system, with the detection of small changes in internal temperature leading to appropriate effector responses. In humans, the maintenance of a constant internal temperature depends on vasomotor control of the cutaneous circulation and sudomotor control of sweating and shivering, with nonshivering thermogenesis also contributing in neonates. Heart rate is also considered to be a thermoregulatory effector. Results from experiments in animals and inferences from pathological lesions of the human brain suggest that the preoptic region and hypothalamus play an important role in the control of thermoregulatory mechanisms (see ref. 1 for review). Electrophysiological recordings from the preoptic area have identified cells that respond directly to changes in temperature. Almost all the cells described in these studies increase their level of activity in concert with increases in temperature. Cells responsive to cooling of the hypothalamus have been described only infrequently (2).The capacity of the hypothalamus to integrate cutaneous thermal afferent information in thermoregulatory processes is a matter of debate. Concurrent measurement of the elec...