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Identifying factors that determine the successful transmission of HIV-1 may help enable the development of better prevention measures. This is what makes the findings of Carlson et al. (1) so relevant. On page 178 of this issue, the authors provide evidence for a bottleneck in HIV-1 transmission that selects for high-fitness viruses. Fitness in this analysis would be reflected either in the infectiousness of each viral particle or in the number of particles produced by an infected cell (burst size). Thus, this fitness bottleneck would act during infection of the first cell or during the first few rounds of local viral replication at the site of transmission where the infection could be extinguished.