In a recent 20-year Danish survey, Neisseria meningitidis phenotypes B:15:P1.7,16 and C:2a:P1.2,5 were associated with an increased case-fatality rate of meningococcal disease - 15% and 23% - compared to the case-fatality rate of 8% for any other strain. The aim of the present study was to investigate (i) the mutual genetic relatedness of strains with phenotype B:15:P1.7,16, phenotype C:2a:P1.2,5 or serologically related phenotypes; (ii) the changes in the prevalence of distinctive clone complexes over time; and (iii) whether distinctive clone complexes are associated with an increased case-fatality rate. During the period 1980-1999, 181 of a total of 315 invasive strains obtained in North Jutland County, Denmark, were chosen on the basis of serological characteristics for characterization by multilocus enzyme electrophoresis and ribotyping. Two major complexes were identified on the basis of electrophoretic type (ET): the ET-4/23 complex ( n=111), which included all B:15:P1.7,16 strains ( n=100), and the ET-15/25 complex ( n=44), which included all C:2a:P1.2,5 strains ( n=31). Two ribotype complexes were identified within the ET-4/23 complex and one within the ET-15/25 complex, all of which were designated clone complexes. All three clone complexes were associated with an increased case-fatality rate (13-20%). The results show that, among invasive Neisseria meningitidis B:15:P1.7,16, C:2a:P1.2,5 and phenotypically related strains, three distinctive clone complexes are more virulent than any other ET/ribotype combination.