To quantify the host genetic component of meningococcal disease (MD) susceptibility, the sibling risk ratio (lambdaS) was calculated as the ratio of observed MD cases among 845 siblings of 443 UK Caucasian cases to that expected, calculated from age-calendar year specific rates for England and Wales. Twenty-seven siblings contracted MD compared with an expected 0.89, generating a lambdaS value of 30.3. Overestimation of lambdaS due to Neisseria meningitidis exposure was minimized by excluding siblings with MD onset within set time points of the index case. Irrespective of whether siblings contracted MD more than 1, 3, 6, 9 or 12 months after the index case, the lambdaS varied slightly (lambdaS range: 8.2-11.9), suggesting that host genetic factors may contribute approximately one third of the total lambdaS. Social class distribution did not differ between MD cases and the general population of England and Wales. This study is the first to calculate lambdaS for MD and establishes that susceptibility to MD has a significant host genetic component.