During the June 1998 heat wave in New Orleans, 8 patients came to the emergency department of a large public hospital over a 14-day period. They were subsequently admitted to the intensive care unit with a diagnosis of heat stroke. On each of these days, the ambient temperature exceeded 33.3 degrees C (91.9 degrees F). Although the highest recorded temperature was only 35.6 degrees C (96 degrees F), the heat index reached a high of 44.5 degrees C (112 degrees F). Weather-related heat illnesses are well documented, but the reports rarely address contributing medications or drugs. In this series, 6 patients (75%) had been using medication or drugs known to induce or worsen hyperthermia. A seventh patient had been prescribed a phenothiazine, but actual use could not be established. An eighth patient had an unidentified agent detected on toxicologic screening. The most common drug identified was cocaine. Other drugs included diphenhydramine, tricyclic antidepressants, and phenothiazines. Six patients (75%) had rhabdomyolysis; 3 of them also had disseminated intravascular coagulation. There were 2 deaths, yielding a 25% mortality rate.