I. PHYSIOLOGICAL SIGNIFICANCE A. Significance of Adaptations to Environment The ability of an animal to adapt to repeated bouts of physical exercise over a period of weeks such that exercise capacity is improved is termed physical training. Some of the inherent mechanisms that are crucial for adaptation to changes in the environment likely carry over to some of the adaptations occurring because of physical training. Prosser (316, 317) has written that cellular, organ, and systemic alterations that favor survival of an animal to an environmental change are said to be adaptive. Physical exercise, like environmental change, disrupts the milieu interieur. Fisher (103) has emphasized that biochemical and physiological adaptations to a changed environment or physiological stimulus fall into two categories based on their duration . Cellular, organ, or systemic alterations that occur on the same time scale as a single exercise bout are said to be acute exercise responses. On the other hand, changes in cells, organs, or systems that persist for appreciable periods after or as a consequence of physical training are said to be exercise adaptations. A function of exercise adaptation seems to be to minimize disruption of homeostasis during an exercise bout. It is this better maintenance of the milieu interieur by the exercise adaptations that favors the functional effectiveness of the animal beyond the resting state. Less disruption in homeostasis permits the animal or human to undergo physical work for longer durations at the same absolute power before fatigue. This review considers molecular and cellular responses to exercise that may signal molecular and cellular adaptations during physical training. B. Significance of Adaptations to Exercise This review is organized to use some of the known causes of fatigue during physical exercise as links between molecular and cellular changes that occur as a result of physical training and the chronic adaptations that are characteristic of physical training. One can speculate that adaptations that improved an animal's work capacity enhanced its survival. The genetic ability to alter exercise performance through physical training has not been lost along the evolutionary scale. Consequently, not all known molecular and cellular changes to exercise are considered here ; this is because their function may not yet be recognized to be associated with adaptations that ameliorate fatigue. In addition, this review does not repeat in great detail material that is available in other reviews. There are 11,689 documents for the Medline MESH word "exertion," Medline's term for exercise, between 1984-1989, inclusive. To the reader unfamiliar with the causes of fatigue during physical exertion, enough description has been given (Table 1) to permit understanding of the physiological significance of the molecular and cellular events. A more detailed review on fatigue is available (108) . In addition, the reader is referred to earlier reviews that have comprehensively documented biochemical responses to a single exercise bout and biochemical adaptations of muscle to physical training.