BACKGROUND/AIMS: Although the importance of genetic susceptibility to inflammatory bowel disease (IBD) has been established by epidemiological studies, the genes involved remain poorly understood. The aim of this study was to assess the role of single nucleotide polymorphisms of tumor necrosis factor-alpha(TNF-alpha) and interleukin-10 (IL-10) genes in genetic susceptibility of IBD. METHODS: Blood samples were obtained from 91 patients with ulcerative colitis (UC), 63 patients with Crohn's disease (CD), and 200 healthy controls (HC). DNA was extracted from blood leukocytes for IL-10 and TNF-alpha genotyping by single base extension reaction. Genotypes and allelic frequencies were compared between IBD patients and HC, and among subgroups of the patients. RESULTS: The frequency of -308A allele of TNF-alpha was significantly lower in CD patients than in HC (p=0.005). The frequency of -238A allele of TNF-alpha was significantly higher in CD patients with perianal lesion than those without perianal lesion. On the other hand, the frequency of -308A allele of TNF-alpha was significantly higher in ANCA-positive IBD patients than ANCA-negative IBD patients. There were no significant differences in allelic frequencies in the promoter region of IL-10 between IBD patients and HC. CONCLUSIONS: The TNF-alpha gene polymorphisms at positions -308 and -238 may have influences on the susceptibility to CD or the behavior of CD.