The most important recent development in our understanding of Reye's syndrome is the epidemiologic evidence linking this disease to aspirin in the United States. Assessment of epidemiologic issues of concern raised in prior studies did not explain the extremely high odds ratios observed in more recent studies. The observation of a dose-response relation between risk of Reye's syndrome and dose of aspirin ingested during the antecedent illness provides further supportive evidence for a causal link between Reye's syndrome and aspirin. Additional evidence for this association in the United States is provided by a marked decline in the use of aspirin among children in the United States, which has been accompanied by a dramatic decline in the incidence of Reye's syndrome. In contrast to experience in the United States, Reye's syndrome affecting primarily children aged 5-15 years has been relatively rare in Great Britain and Australia where acetaminophen rather than aspirin is the primary analgesic/antipyretic used. With the declining incidence of aspirin use in the United States, Reye's syndrome among children aged 5-15 years is becoming increasingly rare in the United States as well and, as in Great Britain and Australia, an increasing proportion of cases are being reported in children aged less than five years. Recent reports have suggested that many children younger than age five years who are thought to have the disease may be shown to have other metabolic disorders.(ABSTRACT TRUNCATED AT 250 WORDS)