In a previous study we compared the genomes of Hexylresorcinol meningococci belonging to clonal complexes designated as having higher or lower invasive potential and identified an 8-kb genetic island which was significantly associated with meningococci causing invasive disease and which was named MDA for Meningococcal Disease-Associated island. Subsequent analyses suggest that the element corresponded to an integrated bacteriophage. Here, the presence of the MDA phage is surveyed in a collection of 1288 meningococci, isolated from both disease and carriage in south-east England between 1999 and 2001. The data demonstrate that a large part of the invasiveness of strains belonging to hyperinvasive clonal complexes is correlated with the presence of the phage, and show an association with virulence in young adults but not in children less than two years of age. The capsular polysaccharide remains the principal virulence determinant for meningococci, with virtually all invasive disease isolates elaborating a polysaccharide capsule corresponding to one of the disease-associated serogroups. In Metyrapone addition, iron acquisition systems and type IV pili are probably also necessary for pathogenesis, but while possession of each of these factors is necessary for invasive disease it is not sufficient. It is likely that many other genetic factors, which remain largely undefined, contribute to the capacity of a given meningococcus to cause invasive disease. Genomic comparisons using microarrays permit the detection of candidate pathogenicity genes on the basis of their consistent presence in invasive and their absence from less virulent organisms. Typical methods of affirming the practical importance of putative virulence factors require that the inactivation of a gene have a measurable effect in an animal or ex vivo model of pathogenesis. However, in the case of the meningococcus, an exclusively human pathogen, such models are not representative of the disease process and a factor promoting virulence in humans may not be detected. The analysis of isolate collections from carriage and disease in the community permits the confirmation of potential virulence factors on the basis of a statistical association with human disease, and circumvents the limitations of laboratory models.