Understanding bacterial population genetics is vital for interpreting the response of bacterial populations to selection pressures such as antibiotic treatment or vaccines targeted at only a subset of strains. The evolution of transmissible bacteria occurs by mutation and localized recombination and is influenced by epidemiological as well as molecular processes. We demonstrate that the observed population genetic structure of three important human pathogens, Streptococcus pneumoniae, Neisseria meningitidis, and Staphylococcus aureus, can be explained by using a simple evolutionary model that is based on neutral mutational drift, modulated by recombination, and which incorporates the impact of epidemic transmission in local populations. The predictions of this neutral ''microepidemic'' model are found to closely fit observed genetic relatedness distributions of bacteria sampled from their natural population, and it provides estimates of the relative rate of recombination that agree well with empirical estimates. The analysis suggests the emergence of neutral bacterial population structure from overlapping microepidemics within clustered host populations and provides insight into the nature and size distribution of these clusters. These findings challenge the assumption that strains of bacterial pathogens differ markedly in relative fitness. infinite-alleles model ͉ multilocus sequence typing ͉ recombination I t is now accepted that bacteria do not conform to the clonal model of evolution (1). The importance of recombination has become increasingly clear in recent years, both as a fundamental process in strain diversification (2) and as a mechanism by which strains acquire virulence factors or resistance determinants (3). Homologous recombination in bacteria involves the replacement of a small segment of the bacterial chromosome (a few kilobases) with the corresponding region from another isolate (2). The frequency of these localized recombinational events may be extremely rare, resulting in species that are highly clonal [e.g., Mycobacterium species (4, 5)], or extremely frequent, resulting in species that are almost completely nonclonal [e.g., Helicobacter pylori (6)]. Consequently, theoretical approaches developed for exclusively sexual or asexual organisms are inappropriate, and, at present, there is no general theory reconciling these variable properties of bacteria. The problem is further complicated by serious sampling biases arising as a result of overrepresentation of disease isolates or antibiotic-resistant isolates in clinical strain collections (1). This problem is especially acute for some species, including Streptococcus pneumoniae, Staphylococcus aureus, and Neisseria meningitidis, which we focus on here and which are ''accidental'' pathogens in that healthy carriage is common, with disease a rare outcome. Finally, the host population structure will influence transmission and needs to be accounted for when considering bacterial population structure: Spread of directly transmitted bacteria within a ...