In the case reported, fatal hyperpyrexia resulted from massive doses of chlorpromazine combined with benztropine mesylate given to a paranoid schizophrenic admitted for increased psychotic symptoms. Phenothiazines disturb the thermoregulatory mechanism and also exert anticholinergic effects peripherally, including sweating. The goal of treatment of drug-induced hyperpyrexia is to reduce oxygen demand and core temperature. Ice water soaked towels, fanning, thermal blanket, or immersion in an ice bath can be used. Oxygenation will help combat further tissue anoxia. Severe acidosis may be present and must be corrected with sodium bicarbonate after arterial pH determination. Vasoconstrictors should be avoided if shock is present.