Recently it has been reported that naturally occurring inhibitors of tumor necrosis factor alpha (TNF-alpha) were demonstrated in urine of some acute febrile patients. We investigated whether TNF-alpha inhibitory activity in urine increases during acute Kawasaki disease (KD). TNF-alpha inhibitory activities in urine were measured by a cytotoxicity assay on the TNF-susceptible cell line L929. KD patients had increased TNF-alpha inhibitory activities in urine during the acute stage and returned to a normal range during the convalescent stage. Our results suggest that the TNF-alpha inhibitor in urine is part of the regulatory system of TNF-alpha, which might be responsible for vascular injury during acute KD.