Although recombination in HIV has been shown to occur at all phylogenetic levels (intra-and inter-subtype, as well as inter-group, reviewed in reference [18] ), the most widely noted impact of recombination on the genetic diversification of this virus is the frequent natural occurrence of inter-subtype recombinants in parts of the world where multiple subtypes co-circulate [19] [20] [21] [22] . When the same inter-subtype recombinant is transmitted between multiple individuals, and has therefore the potential to be of epidemiological significance, it is termed a Circulating Recombinant Form (CRF) [17] . As with the HIV-1 subtypes, CRFs form distinct clusters in phylogenetic trees and some of them contribute substantially to the pandemic. Sufficient inter-subtype recombinant sequences have been sampled to permit the detailed characterisation of variation in the locations of breakpoints both within individual genes [22, 23] , and entire genomes [24, 25, 32] . This makes HIV a particularly useful model for studying the forces that shape pathogen populations within the context of global epidemics. Here we focus on recombination within the envelope gene (env). This gene encodes two polypeptides (gp120 and gp41) that form a heterodimer at the surface of the viral particle. Trimers of these heterodimers are the functional units that are responsible for binding to the cellular receptors and co-receptors and ultimately lead to viral entry into target cells [26] . The two protein products of env are also the targets of all the neutralising antibodies identified to date [27] . By using a tissue culture system to characterise inter-subtype recombinants generated within env in the absence of selection, and assaying the functionality of recombinant genes, we produce an empirical model of HIV recombination that accurately describes recombination patterns found in viruses sampled throughout the HIV pandemic.