Reye syndrome is a distinct, reversible syndrome occurring after an antecedent viral infection, characterized by severe noninflammatory encephalopathy and fatty degeneration of the liver Once the link between antecedent aspirin exposure and the onset of Reye syndrome was established, the incidence has declined to about two cases per year Isolated case reports continue to be described, indicating the need to continue to consider Reye syndrome when evaluating patients with the typical clinical presentation Most of the clinical features of Reye syndrome, including lactic acidosis, elevated fatty acids, nitrogen wasting, hyperammonemia, cellular fat accumulation, and cytotoxic cerebral edema, may be explained in the context of primary mitochondrial damage A biphasic clinical history is remarkably constant First, the child has a history of a recent, usually febrile, illness that is waning or has resolved Approximately 90% of the children have an antecedent upper respiratory tract infection Varicella virus or influenza B infections have been most associated The abrupt onset of protracted vomiting usually starts within week following the prodromal illness The vomiting is unresponsive either to restriction of oral intake or to antiemetic therapy Coincident with the onset of vomiting (or shortly thereafter), signs of encephalopathy appear At first, encephalopathy may be manifested by unusual quietness or disinterest However, a rapid sequential progression to irritability, combativeness, confusion, disorientation, delirium, stupor, and coma may occur Seizures are a late sign in older children but may occur during early stages of encephalopathy in infancy (usually secondary to hypoglycemia) In the ED, patients are usually afebrile Tachycardia and hyperventilation commonly occur At the initial presentation, only 50% of patients have hepatomegaly The liver usually increases in size during the first 24 to 48 hours after the diagnosis is made The absence of jaundice and scleral icterus is characteristic and is the major mitigating clinical sign against hepatic encephalopathy secondary to acute fulminant hepatitis Despite evidence of encephalopathy, no focal neurologic signs or signs of meningeal irritation are apparent The hallmark of the acute encephalopathy of Reye syndrome is the associated evidence of liver abnormality The levels of transaminases (ALT and AST) and blood ammonia are almost always elevated at the time of the onset of protracted vomiting The range of transaminase elevation is highly