Exercise in hot ambient severely disrupts body homeostasis and enhances autonomic and neuroendocrine responses to exercise. Also, high levels of exercise-induced hyperthermia seem to be able to affect cerebral electrical activity and the ability of central nervous system to recruit the skeletal muscles. Thus, it is possible that exercise in the heat also induces subtle changes in the central pathways that regulate hypothalamic function that may be revealed by a subsequent metabolic challenge. PURPOSE To determine the effect of exhausting exercise in the heat on cardiovascular and neuroendocrine responses to an acute hypoglycemic insulin challenge (IC) conducted after exercise. METHODS Twelve active males underwent a hypoglycemic insulin challenge (0.15 mIU/kg) 2.5 h after 60 min of cycle exercise (E)(60% peak power) in the heat (35°C; 20% rh) or after rest (R). Blood samples were taken during IC to measure plasma glucose (GLU), lactate (LAC), prolactin (PRL) and cortisol (CORT). Heart rate (HR) and mean blood pressure (MBP) were obtained by ECG recording and automated sphygmomanometer, respectively. Trial comparisons were made using twoway ANOVA with repeated measures. RESULTS Rectal temperature rose from 36.98 ±0.08°C at rest to 38.35 ±0.11°C at the end of exercise (p<0.001) and at this point RPE scores attained 16.5 ±0.8 units. GLU during IC reached similar nadirs in both trials with values below 2.2 mmol/L. Plasma LAC during IC increased above baseline to a similar extent in both trials, with peak values of 2.33 ±0.20 mmol/L and 2.65 ±0.26 mmol/L in E and R, respectively. At IC onset, plasma PRL and CORT had recover from levels at the end of exercise in the heat to baseline levels. Peak values of plasma PRO and CORT during IC were unchanged by prior exercise and amounted to around 5- and 2.5-fold baseline levels, respectively. HR and MBP had a similar biphasic change in the two trials, increasing during the first hour post insulin injection and declining to below baseline levels thereafter. CONCLUSION Exhaustive exercise in the heat does not induce acute changes in heart rate, blood pressure and hormonal reactivity to a hypoglycemic challenge, revealing hypothalamic and pituitary robustness to the effects of acute exercise in the heat. Partially supported by EU and Portuguese government grant PRAXIS XXI BD/21295/99.