An alternative to such methods consists in molecular epidemiological studies in the community, involving the analysis of isolates from human Theaflavin disease and asymptomatic carriage. These studies are founded on the expectation that the presence of a Liranaftate virulence gene is correlated with a higher probability of being isolated from invasive disease. We hypothesised firstly that a virulence gene would be overrepresented in the hyperinvasive clonal complexes and then secondly that, if the relation were causal rather than simply clonal, there would exist within the hyperinvasive complexes an association of the element with invasive disease. We previously identified a candidate virulence factor, the MDA prophage, by whole genome comparisons of well-characterised isolates from an epidemic situation in 1993 in the Czech Republic. Here the association of the MDA phage with disease is examined in an independent data set comprising 1288 isolates from south-east England. A preliminary analysis of the results confirmed the association of the element both with disease and with certain clonal complexes, but did not permit the distinction between the possibilities that the association of the prophage with disease was due to the presence of a second virulence factor overrepresented in the hyperinvasive clonal complexes, or that the prophage was one of the reasons for which the hyperinvasive clonal complexes were more likely to cause disease. This question was addressed by evaluating the effect of the phage on the relative virulence of each clonal complex separately. The frequent horizontal genetic exchange between strains of this naturally competent species leads to genetic differences between the meningococci comprising a given clonal complex and to differences in their pathogenic potential. This heterogeneity provides the opportunity to analyse the association of a candidate virulence gene with disease. In this way between 21 and 45% of the disease-causing potential of the common hyperinvasive clonal complexes could be attributed to the possession of the MDA phage, or to factors accessory to the phage, hence supporting the hypothesis that the element acts, in concert with other virulence factors, to increase the pathogenic potential of meningococci.