The VNTR polymorphism in intron 2 of the interleukin-1 receptor antagonist (IL-1RA) gene has been shown associated with ulcerative colitis (UC) in some populations. This study aimed to assess the relationship between the IL-1RA polymorphism and UC in a Japanese population. Genotyping was carried out with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method for 468 DNA specimens from 239 healthy volunteers and 229 patients with UC. Genotype distribution was compared between cases and controls, and association of patients' genotype with clinical parameters was evaluated. No significant difference of genotype distribution was found between UC patients and healthy controls. However, when the relation of the carriage rate of allele 2 with clinical parameters was evaluated by Fisher's exact test, it was found that the allele 2 carriage rate was higher in patients with lower ages at diagnosis (< 30) than those with higher ages (> or =30) (odds ratio (OR), 5.049; 95% confidence interval (CI), 1.667-15.288; P= 0.0020). In addition, it tended to be higher in patients with pancolitis type than those with other types restricted to the distal or left-sided colon (OR, 3.005; 95% CI, 1.186-7.616; P=0.0256). These data suggest that the IL-1RA polymorphism is associated with UC with younger age at diagnosis.