In this study of patients with confirmed meningococcal disease, we examined the frequency of well-described variants in the IL-1 gene cluster. We restricted our analysis to two polymorphic sites (IL1B[−511] and IL1RN[+2018]) because we previously found an effect of IL-1 genotype in meningococcal disease (which was confined to these two SNPs) in a separate and smaller sample for which genotyping was done at several sites in the IL-1 gene cluster (13). In the current study, we sought to exclude confounding effects of age, infecting serogroup, and socioeconomic status. With these variables included in a logistic regression model, we found that IL1B(−511) was associated with outcome; patients carrying the common allele at this site were more likely to survive. However, among the group carrying the common allele at IL1B(−511), we found an additional effect on likelihood of survival, which was conditional on genotype at IL1RN(+2018). Patients carrying the rare allele at IL1RN(+2018) were less likely to survive than those who did not carry the rare allele. In our previous, smaller study of 276 patients who were between 4 and 70 years of age, 39 died, and the association between death and genotype at IL1B(−511) was significant. The composite genotype consisting of heterozygosity of IL1B(−511), together with homozygosity of the common allele at IL1RN(+2018), was significantly associated with survival. Therefore, the current study confirms a relationship between allelic variation of the IL-1 gene cluster and meningococcal disease. The study sample is large enough to provide more detailed information about this relationship and includes patients of all ages.