Innate immunity has been mostly neglected in favor of HIV-specific immunity in HIV vaccine studies. CCL3 production should be considered a correlate of protective immunity. A desired response would be sufficient production of CCL3 at the site of HIV and vaccine encounter. It is imperative to delineate the precise functions of CCL3 in the immune response to HIV, aside from its noncytolytic inhibitory effect on HIV, as the ability of CCL3 to drive the development of adaptive immunity might be the crucial factor in overall protection. Many important questions arise, given the findings outlined here. How should HIV vaccines be designed? How can people who would be poor responders to vaccines (deficient CCL3 producers) be identified? How can the genetically encoded loss of function be overcome, and how can molecules be identified that can compensate for this? Innate immunity must become a more integral component of studies of HIV vaccines, as understanding the interaction between innate and adaptive immunity may hold the key to understanding what constitutes protective immunity to HIV. Studies of uninfected infants born to HIV-infected mothers offer a unique human experimental model for extending the understanding of such phenomena.