Meningococcal disease may present as sepsis, meningitis or a combination of bo th. Impaired fibrinolysis and massive elevation of the plasminogen activator inh ibitor-1 (PAI-1) is a characteristic feature of meningococcal sepsis. Previous ly, an association between mortality and the functional 4G/5G promoter polymorph ism of the PAI-1gene in a cohort of UK and Dutch children with meningococcal se psis was reported. We carried out a prospective, multicentre study to investigat e the association of the 4G/5G PAI-1 polymorphism, diagnosis, and outcome in me ningococcal disease in a Central European and UK population. Blood samples and c linical information of 347 previously healthy children with meningococcal infect ion were collected from 95 paediatric hospitals in Germany, Switzerland, Italy, the United Kingdom, and Austria from 2000 until 2002. Mortality was significantl y associated with the 4G/4G genotype (12 of 90 (13%) vs. 15 of 240 (6%), P =0. 037), resulting in an odds ratio of 2.31. The diagnosis of sepsis (independent o f symptoms of meningitis) was significantly more frequent in carriers of the 4G/ 4G genotype (P =0.01), resulting in an odds ratio of 2.21 to develop sepsis. Men ingitis was not associated with the PAI-1 4G/5G polymorphism, and allele freque ncies were similar in patient and control groups. Conclusion:Our data show a cor relation between the 4G/4G genotype in the plasminogen activator inhibitor-1 ge ne and poor outcome in children with meningococcal infection. In addition, 4G ho mozygous patients were prone to develop sepsis. We found no influence of the pla sminogen activator inhibitor-1 polymorphism on the susceptibility to invasive m eningococcal infection. Meningococcal disease may present as sepsis, meningitis or a combination of bo th. Impaired fibrinolysis and massive elevation of the plasminogen activator inh ibitor-1 (PAI-1) is a characteristic feature of meningococcal sepsis. Previous ly, an association between mortality and the functional 4G / 5G promoter polymorph ism of the PAI-1 gene in a cohort of UK and Dutch children with meningococcal sepsis was reported. We carried out a prospective, multicentre study to investigat e the association of the 4G / 5G PAI-1 polymorphism, diagnosis, and outcome in me ningococcal disease in a Central European and UK population. Blood samples and cinical information of 347 previously healthy children with meningococcal infect ion were collected from 95 pediatric hospitals in Germany, Switzerland, Italy, the United Kingdom, and Austria from 2000 until 2002. Mortality was significantl y associated with the 4G / 4G genotype (12 of 90 (13%) vs. 15 of 240 (6%), P = 0. 037), resulting in an odds ratio of 2 . The diagnosis of sepsis (independent of symptoms of meningitis) was significantly more frequent in carriers of the 4G / 4G genotype (P = 0.01), resulting in an odds ratio of 2.21 to develop sepsis. Men ingitis was not associated with the PAI-1 4G / 5G polymorphism, and allele freque ncies were similar in patient and control groups. Conclusion: Our data show a cor relation between the 4G / 4G genotype in the plasminogen activator inhibitor-1 ne ne and poor outcome in children with meningococcal In addition, 4G ho mozygous patients were prone to develop sepsis. We found no influence of the pla sminogen activator inhibitor-1 polymorphism on the susceptibility to invasive m eningococcal infection.