Exertional heat stroke (EHS) is an acute life-threatening emergency that necessitates the immediate institution of cooling measures. Reported here is a case of EHS in a nonacclimatized young woman who was undergoing strenuous exercise. The patient developed many of the characteristic features of EHS, including central nervous system disturbances, lactic acidosis, rhabdomyolysis, coagulopathy, and abnormal myocardial conduction. While EHS is relatively common in young men, the condition is rare in women. This case presentation addresses gender differences in the response to the thermal stress of intense physical activity.