Ninety-seven Reye's syndrome (RS) cases in Ohio children with onsets from December 1978 through March 1980 were studied for medication use during their pre-RS illness. They were matched with 156 control subjects for age, race, sex, geographic location, time, and type of illness. Only the use of aspirin was reported by significantly more cases (97%, 94/97) than controls (71%, 110/156) during the pre-RS matched illness. Using a multiple logistic model to control for the presence of fever, headache, and sore throat statistically, the difference in aspirin use remained significant. Conversely, fewer cases (16%) took medications containing acetaminophen than controls (33%). In 87% of the cases receiving aspirin, their maximum daily dosage did not exceed recommended levels, but their doses were higher than those of controls receiving aspirin. No relationship was found between dosage and stage of RS encephalopathy.