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Temperature regulation is a homeostatic feedback control system that ensures deep body temperature is maintained within narrow limits despite wide variations in environmental conditions and activity-related elevations in metabolic heat production. Extensive research has been performed to study the physiological regulation of deep body temperature. This review focuses on healthy and disordered human temperature regulation during heat stress. Central to this discussion is the notion that various morphological features, intrinsic factors, diseases, and injuries independently and interactively influence deep body temperature during exercise and\/or exposure to hot ambient temperatures. The first sections review fundamental aspects of the human heat stress response, including the biophysical principles governing heat balance and the autonomic control of heat loss thermoeffectors. 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