Background and Purpose: Tumor necrosis factor-alpha (TNF-α) has been shown to play a central role in the pathogenesis of vasculitis in Kawasaki disease (KD). We investigated the serum levels of TNF-α and soluble TNF receptor 1 (STNFR1) levels, and genetic polymorphisms of the TNF-α promoter gene in children with KD to delineate the genetic basis of KD. Methods: A total of 18 children ( 12 boys and 6 girls ) with KD were studied, 9 of whom had the complication of coronary artery lesion (CAL) within 30 days after the onset of symptoms. Serum levels of TNF-α and STNFR1 were assayed by enzyme-linked immnosorbent assay, and DNA polymorphisms of the 5’ flanking region of TNF-α promoter gene at position -308 [guanine (G) to adenine (A)] and -238 ( G to A ) were studied by direct nucleotide sequencing. Results: The serum TNF-α level in KD patients was 113 ± 209.9 pg/mL (range, 2.0 to 756.9 pg/mL; median, 24.7 pg/mL normal, ＜ 10 pg/mL). The serum levels of STNFR1 in KD (4255 ± 2425 pg/mL) were higher than those of the control group (160 ± 116 pg/mL). Allele frequencies of -308A and -238A were 11.1% and 0% in the KD patients, and 0% and 3.1% in the control group. Neither TNF-α promoter polymorphism nor any significant risk factor for CAL was identified in KD patients. One patient, who was homozygous for -308A, showed the highest TNF-α level and elevated STNFR1 level but had no evidence of CAL. Positive correlations were found between serum levels of STNFR1 and C-reactive protein ( r = 0.731 , p = 0.007 ) , and between STNFR1 and leukocyte counts at admission ( r = 0.620, p = 0.008 ). Conclusions: Increased serum levels of TNF-α and STNFR1 were found in KD patients but there was no correlation between these levels. The relationship between the pathogenesis of KD and TNF-α gene promoter -308G to A mutation towards cytokine production remains to be clarified.