It has been recently reported that CD8(+) T cells from healthy human peripheral blood express the tolerogenic HLA-G molecule originally described in trophoblasts. The majority of these CD8(+)HLA-G(+) cells exhibit a naïve phenotype and are FoxP3 negative, and they have been classified as a novel subset of regulatory T cells based on their potent suppressive function. We have investigated if this new cell population is expanded during HIV-1 infection. The results presented here show an increase in the percentage of CD8(+)HLA-G(+) cells within the total CD8 T-cell population in HIV-1(+) patients. As in healthy controls, these CD8(+)HLA-G(+) are mostly naïve T cells. However, we have also observed that only in HIV-1-infected patients are there effector and effector memory cells that express HLA-G.