We investigated 49 children (33 boys), mean (±SD) age 2.6±1.8 years (range 8 months to 8 years), who had Kawasaki disease treated with acetylsalicylic acid (ASA) 30 to 180 mg/kg. There was good correlation between salicylate doses and serum concentrations (r=0.69, P<0.01); however, large variability existed. With doses <80 mg/kg/day there was not a single therapeutic salicylate serum concentration (>20 mg/dl). In children receiving 100 to 110 mg/kg/day 55% of the serum concentrations were subtherapeutic. The same pattern persisted with doses >120 mg/kg/day; however, 28% of levels were in the toxic range (>30 mg/dl). There was no evidence of salicylate poisoning in the group; three children receiving >100 mg/kg/day had aspirin-induced gastritis. An additional four children, studied prospectively, received ASA 80 to 180 mg/kg/day. The fraction absorbed was 14% to 60%, which may be compared to a normal 85% to 90% absorption. Salicylate renal clearance in these children (7.3 to 21 ml/kg/hr) was lower than in hyperthermic children. Their steady-state serum salicylate concentrations were subtherapeutic (7 to 11.5 mg/dl). The high ASA dose needed to overcome the impaired absorption should be accompanied by frequent monitoring of levels because of the unpredictable changes in absorption.