We have identified a post-entry CCR6-dependent mechanism of inhibition of HIV occurring at an early stage of infection mediated by the induction of the host restriction factor apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G (APOBEC3G). We observed induction of APOBEC3G expression only in CCR6(+) cells, but not in cells treated with the Gi pathway inhibitor pertussis toxin. CCR6 is highly expressed on peripheral blood CD4(+)CCR5(+) memory T cells, and by two populations of CD4(+) T cells within the gut, alpha4beta7(+) and TH(17), that have been implicated in cell-to-cell spread of HIV and enhanced restoration of CD4(+) T cells within gut associated lymphoid tissue (GALT), respectively. This novel CCR6 mediated mechanism of inhibition allows the identification of pathways that induce intrinsic immunity to HIV, which could be useful in devising novel therapeutics that selectively target CCR6(+) cells.