The central body temperature of a man rises gradually during the first half hour of a period of work to a higher level and this level is precisely maintained until the work is stopped; body temperature then slowly declines to the usual resting level. During prolonged work the temperature regulatory center in the hypothalamus appears to be reset at a level which is proportional to the intensity of the work and this setting is independent of environmental temperature changes ranging from cold to moderately warm. In hot environments the resistance to heat loss may be so great that all of the increased metabolic heat of work cannot be dissipated and the man's central temperature will rise above the thermostatic setting. If this condition of imbalance is continued long enough heat stroke will ensue. We have found that in a 3 mile race lasting only 14 minutes on a hot summer day a runner's rectal temperature may rise to 41.1°C., with heat stroke imminent. The physiological regulation of body temperature of men in warm environments and during the increased metabolic heat production of work is dependent on sweating to provide evaporative cooling of the skin, and on adjustments of cutaneous blood flow which determine the conductance of heat from the deeper tissues to the skin. The mechanisms of regulating these responses during work are complex and not entirely understood. Recent experiments carried out in this laboratory indicate that during work, sweating may be regulated by reflexes originating from thermal receptors in the veins draining warm blood from the muscles, summated with reflexes from the cutaneous thermal receptors, both acting through the hypothalamic center, the activity of which is increased in proportion to its own temperature. At the beginning of work the demand for blood flow to the muscles results in reflex vasoconstriction in the skin. As the body temperature rises the thermal demand predominates and the cutaneous vessels dilate, increasing heat conductance to the skin. Large increments in cardiac output and compensatory vasoconstriction in the abdominal viscera make these vascular adjustments in work possible without circulatory embarrassment.