From the viewpoint of the neurohumoral interaction in the control of body temperature, brain activity under extreme cold was studied by means of EEG observation and electrical stimulation, employing New Zealand white rabbits with chronically implanted bipolar electrodes in the several parts of the brain. During experiment, rabbits were free to move around on the observation table or in the cold box under constant illumination.<BR>The results were as follows:<BR>The EEG activity showed the following alterations during exposure to cold (at a temperature of 20°C below zero for a period of 12 hours).<BR>1. Exposure to the extreme cold brought about an enhancement of EEG activity in the medial preoptic area, ventromedial nucleus of the hypothalamus, posterior hypothalamus, periventricular stratum, hippocampus, medial amygdala, lateral septum and central grey, and suppression of EEG activity in the lateral preoptic area, lateral hypothalamus, lateral amygdala and medial septum. EEG recorded from the arcuate nucleus and its adjacent region did not show any notable change resulting from cold exposure. To summarize the above results, EEG of the areas belonging to the so-called sympathetic zone showed elevated activity under extreme cold. At the same time, some areas belonging to the so-called parasympathetic zone and the limbic system also showed an activated pattern during cold exposure. EEGs were recorded from the brain of immature rabbits of 14 to 40 days of age. It was suggested that the amygdala was the earliest center to develop for the regulation of body temperature. In the later stages of development the hippocampus takes the place of the amygdala in the thermo-regulatory mechanism.<BR>2. Repetitive cold exposure (20°C below zero for 12 hours per a day) and simultaneous EEG recording were carried out for a period of 7 or 10 days in summer. The change observed in the hippocampus, amygdala, medial preoptic area, periventricular stratum, ventromedial hypothalamus and posterior hypothalamus observed at the initial exposure gradually decreased, until the EEG activity in these areas was hardly influenced by the 5th or 10th exposure to cold. The activity of the limbic areas tended to lose reaction to cold exposure earlier than the latter.<BR>3. In order to elucidate the relation of increased activity in various parts of the brain to body temperature, a stimulation experiment was performed. Stimulation consisted of monophasic square wave pulses delivered unilaterally for one hour, 60 sec. on and 60 sec. off, at 0.5 msec. duration, 60 cps. The stimulation on each part of the brain caused a rise in rectal temperature. The change was divided into immediate effect (Effect during stimulation) and delayed effect (effect after stimulation). Immediate effect (rise of rectal temperature by 0.3 to 0.8°C) was observed by the stimulation of regions included in the so-called sympathetic zone of the hypothalamus such as the medial preoptic area, ventromedial hypothalamus and posterior hypothalamus and some areas of limbic system such as the amygdala, lateral septum and central grey. On the other hand, delayed effect was observed by the stimulation of the medial preoptic area, ventromedial hypothalamus (so-called sympathetic zone), lateral hypothalamus, arcuate nucleus (so-called para sympathetic zone), hippocampus, amygdala, lateral septum and central grey (limbic area). It may be supposed that the immediate effect was caused by neural factors or by fast-acting substances like epinephrine, and that the latter was brought about by slow-acting factors such as ad renocortical hormones or thyroid hormone.<BR>4. In order to clarify the significance of the delayed effect which might play an important role in the prolonged exposure to cold, electrical stimulation of the limbic area was carried out in adrenalectomized rabbits and thyroidectomized rabbits.