Objective: To quantify the similarity (or lack of) between the phylogenetic substructure of HIV-1 groups 0 and M. Methods: Two phylogenetic tree statistics - the subtype diversity ratio (SDR) and the subtype diversity variance (SDV) - were used in conjunction with bootstrap replicates on gag, pol and env sequence alignments of group 0 and M strains. Randomly generated phylogenetic trees were used as a control. Results: We show that, as expected, the established global-group M subtypes have a high degree of phylogenetic symmetry in relation to each other in terms of inter- and intra-subtype diversification. They are significantly different from the substructure present amongst the random trees. To the contrary, the group 0 diversification does not display this highly symmetrical substructure and is not significantly different from the substructure present on randomly generated trees. Phylogenies comprised of group M strains from the epicentre of the HlV/AlDS pandemic, the Democratic Republic of Congo (DRC), exhibit a substructure more similar to group 0 than to global-group M. Conclusions: The substructure present within groups 0 and M is quantifiably different. The well defined clades, the subtypes that characterize group M diversification, are not present in group 0 or amongst group M strains from the DRC. The group M subtypes are thus unique and a signature of pandemic HIV-1. (c) 2007 Lippincott Williams & Wilkins.