We investigated whether a core temperature threshold for hyperthermic hyperventilation is seen during prolonged submaximal exercise in the heat when core temperature before the exercise is reduced and whether the evoked hyperventilatory response is affected by altering the initial core temperature. Ten male subjects performed three exercise trials at 50% of peak oxygen uptake in the heat (37°C and 50% relative humidity) after altering their initial esophageal temperature (T(es)). Initial T(es) was manipulated by immersion for 25 min in water at 18°C (Precooling), 35°C (Control), or 40°C (Preheating). T(es) after the water immersion was significantly higher in the Preheating trial (37.5 ± 0.3°C) and lower in the Precooling trial (36.1 ± 0.3°C) than in the Control trial (36.9 ± 0.3°C). In the Precooling trial, minute ventilation (Ve) showed little change until T(es) reached 37.1 ± 0.4°C. Above this core temperature threshold, Ve increased linearly in proportion to increasing T(es). In the Control trial, Ve increased as T(es) increased from 37.0°C to 38.6°C after the onset of exercise. In the Preheating trial, Ve increased from the initially elevated levels of T(es) (from 37.6 to 38.6°C) and Ve. The sensitivity of Ve to increasing T(es) above the threshold for hyperventilation (the slope of the T(es)-Ve relation) did not significantly vary across trials (Precooling trial = 10.6 ± 5.9, Control trial = 8.7 ± 5.1, and Preheating trial = 9.2 ± 6.9 L·min(-1)·°C(-1)). These results suggest that during prolonged submaximal exercise at a constant workload in humans, there is a clear core temperature threshold for hyperthermic hyperventilation and that the evoked hyperventilatory response is unaffected by altering initial core temperature.