Heat stroke should be considered in the clinical context of environmental heat stress, hyperthermia, and altered mental status. The differential diagnosis includes infection (eg, sepsis, meningitis, encephalitis, malaria, typhoid, tetanus), endocrine disorders (eg, diabetic ketoacidosis, thyroid storm), neurologic disorders (eg, cerebrovascular accident, status epilepticus), and toxicologic causes (eg, anticholinergics, sympathomimetics, salicylates, serotonin syndrome, malignant hyperthermia, neuroleptic malignant syndrome, alcohol or benzodiazepine withdrawal). About 20% of heat stroke patients are hypotensive. Initial diagnostic studies are directed at detecting end-organ damage and excluding other disease processes. Respiratory alkalosis and lactic acidosis are seen in exertional heat stroke; respiratory alkalosis in nonexertional heatstroke. Early laboratory abnormalities associated with exertional heat stroke include hypoglycemia, hypophosphatemia and hypokalemia, elevated liver enzymes due to hepatocellular damage, hypercalcemia and an elevated hematocrit due to hemoconcentration, and elevated creatine phosphokinase and myoglobin from rhabdomyolysis. Laboratory abnormalities of DIC, renal failure develop with time. Obtain an ECG and CXR. Neuroimaging studies and other evaluations (eg, septic workup, toxicology screens) can be individualized as clinically indicated.