Nielsen. Influence of body temperature on the development of fatigue during prolonged exercise in the heat. J. Appl. Physiol. 86(3): 1032-1039, 1999.-We investigated whether fatigue during prolonged exercise in uncompensable hot environments occurred at the same critical level of hyperthermia when the initial value and the rate of increase in body temperature are altered. To examine the effect of initial body temperature [esophageal temperature (T es ) ϭ 35.9 Ϯ 0.2, 37.4 Ϯ 0.1, or 38.2 Ϯ 0.1 (SE)°C induced by 30 min of water immersion], seven cyclists (maximal O 2 uptake ϭ 5.1 Ϯ 0.1 l/min) performed three randomly assigned bouts of cycle ergometer exercise (60% maximal O 2 uptake) in the heat (40°C) until volitional exhaustion. To determine the influence of rate of heat storage (0.10 vs. 0.05°C/min induced by a water-perfused jacket), four cyclists performed two additional exercise bouts, starting with T es of 37.0°C. Despite different initial temperatures, all subjects fatigued at an identical level of hyperthermia (T es ϭ 40.1-40.2°C, muscle temperature ϭ 40.7-40.9°C, skin temperature ϭ 37.0-37.2°C) and cardiovascular strain (heart rate ϭ 196-198 beats/min, cardiac output ϭ 19.9-20.8 l/min). Time to exhaustion was inversely related to the initial body temperature: 63 Ϯ 3, 46 Ϯ 3, and 28 Ϯ 2 min with initial T es of ϳ36, 37, and 38°C, respectively (all P Ͻ 0.05). Similarly, with different rates of heat storage, all subjects reached exhaustion at similar T es and muscle temperature (40.1-40.3 and 40.7-40.9°C, respectively), but with significantly different skin temperature (38.4 Ϯ 0.4 vs. 35.6 Ϯ 0.2°C during high vs. low rate of heat storage, respectively, P Ͻ 0.05). Time to exhaustion was significantly shorter at the high than at the lower rate of heat storage (31 Ϯ 4 vs. 56 Ϯ 11 min, respectively, P Ͻ 0.05). Increases in heart rate and reductions in stroke volume paralleled the rise in core temperature (36-40°C), with skin blood flow plateauing at T es of ϳ38°C. These results demonstrate that high internal body temperature per se causes fatigue in trained subjects during prolonged exercise in uncompensable hot environments. Furthermore, time to exhaustion in hot environments is inversely related to the initial temperature and directly related to the rate of heat storage. hyperthermia; skin blood flow; heart rate; stroke volume IT IS WELL DOCUMENTED that endurance can be impaired in hot compared with temperate climates (10,12,28) and that time to exhaustion is influenced by alterations of the initial body temperature (1,22,32,39). The attainment of a critically high level of body temperature has been proposed as the main factor limiting endurance performance in hot environments (7,28). The observation that trained subjects working at 60% of peak O 2 uptake (V O 2 peak ) in the heat [40°C, 10% relative humidity (RH)] for 9-12 consecutive days improved exercise performance from 48 to 80 min but fatigued at a core temperature of 39.7°C appears to support this notion (28). This large improvement in exercise time t...