ObjectiveReye's syndrome (RS) appeared suddenly in the 1950s and disappeared almost as quickly in the late 1980s. A number of metabolic disorders were discovered in the 1980s that could completely mimic RS. This study was undertaken to reassess the original diagnosis of RS in light of newly described metabolic disorders.InterventionThe medical records of 26 patients who had survived RS and were originally studied in Australia in the 1980s were reexamined 10 yrs later, and families were interviewed to ascertain if the diagnosis had changed. The 49 original patients with RS from Australia were also reanalyzed using more precise diagnostic criteria for RS to ascertain how many of the patients would continue to fit the more precise diagnosis of RS.Measurements and Main ResultsOf 26 original patients with RS who had survived, 18 (69%) were subsequently diagnosed as having other diseases, most commonly inborn errors of metabolism. The most commonly diagnosed metabolic disorder was medium-chain acyl-coenzyme-A dehydrogenase deficiency. Of the 18 patients rediagnosed with diseases other than RS, 15 (83%) are now known to have metabolic disorders.By using more precise diagnostic criteria for RS, none of the original 49 patients with RS could be diagnosed as having certain RS.Only six patients had probable RS, two patients had possible RS, 23 patients had unlikely RS, and 18 patients were excluded as RS cases.ConclusionWith better diagnostic techniques and criteria, most patients originally diagnosed with RS are now known to have metabolic disorders. The disappearance of RS was probably related to the discovery and ability to diagnose inborn errors of metabolism that mimicked RS clinically, biochemically, and pathologically. (Crit Care Med 1999; 27:1582-1587)