Chronic inflammatory bowel diseases (IBDs), specifically Crohn's disease (CD) and ulcerative colitis (UC), have increased significantly in western countries and Japan over the last decade, but very little is known about their pathogenesis. A candidate-gene approach recently identified NOD2/CARD15 as one susceptibility gene from the IBD1 locus on chromosome 16. Alterations in this gene were found in many Caucasian patients with CD; in particular, two nonsynonymous substitutions (R702W and G908R) and a frameshift mutation (1007fs) were shown to be independent risk factors for CD. We investigated DNA from 483 Japanese CD patients to detect those three mutations in NOD2/CARD15 by appropriate genotyping techniques, but found only an R702Q substitution in a single patient. Direct sequencing of DNA from 96 of our patients in the regions containing the three reported major mutations detected no sequence alterations of consequence. Our findings indicate that the NOD2/CARD15 gene is not a major contributor to CD susceptibility in the Japanese population.