PURPOSE: Recently, it was reported that tumor necrosis factor (TNF) and lymphotoxin-alpha (LT-alpha) gene regions might be a susceptible loci to type 1 diabetes in Japanese. The purpose of this study was to investigate the association of TNF and LT-alpha gene polymorphisms with disease susceptibility in Korean children with type 1 diabetes. METHODS: Forty-nine Korean children with type 1 diabetes (29 girls and 20 boys) and 94 healthy Koreans were investigated in this study. Genotyping for -857T/C polymorphism in the TNF promoter region and LT-alpha gene polymorphism were performed by PCR-RFLP (restriction fragment length polymorphism). TNF promoter -1031C/T polymorphism was detected by allele-specific PCR. RESULTS: The distribution of the -857T/C and -1031C/T genotype in the TNF promoter region was not different between diabetic children and the controls. The frequency of TT genotype in the distribution of TNF -1031C/T polymorphism in diabetic children with diabetic ketoacidosis (DKA) at diagnosis was significantly lower than those without DKA (P< 0.05). No significant difference in the distribution of LT-alpha gene polymorphism was observed between diabetic children and the controls. There was no association between clinical characteristics of type 1 diabetes and LT-alpha gene polymorphisms. CONCLUSION: These results suggest that TNF promoter -857T/C and LT-alpha gene polymorphisms are not associated with susceptibility to type 1 diabetes in Korean children. TNF promoter -1031C/T polymorphism might be related to clinical manifestations (DKA) of type 1 diabetes.