The efficacy of high-dose salicylates in reducing the coronary artery involvement of Kawasaki disease was compared in 36 children who received acetylsalicylic acid, 80 to 180 mg/kg/day, and in 18 who did not receive high-dose salicylates during the febrile phase of the disease and whose fever was controlled mainly with acetaminophen. The two groups were comparable with respect to age and body weight. In the acetylsalicylic acid-treated group, the dose was adjusted to meet the therapeutic serum concentration range (greater than or equal to 20 mg/dL). There were significantly more cases of coronary involvement in the nontreated group (50%) than in the salicylate-treated group (16.6%) and of coronary aneurysms (39% vs 3%). During the febrile phase of the disease, salicylate serum concentrations achieved with a given dose were on the average twofold lower than during the nonfebrile phase, owing to impaired absorption of acetylsalicylic acid. It is suggested that despite the difficulty in achieving therapeutic serum concentrations of salicylate during the febrile phase of Kawasaki disease with a dose as high as 100 mg/kg/day, this dose is potentially capable of preventing the associated coronary disease.