Human gammadelta (γδ) T cells play an important role in protective immunity in HIV-1 and simian immunodeficiency virus infection; their role in HIV-2 infection is unknown. To determine the role of γδ T cells in control of plasma viral load and CD4 T-cell count in HIV-1 and HIV-2 infections in West Africa. Thirty HIV-1 and 25 HIV-2 treatment-naive chronically infected individuals, and 20 HIV-seronegative individuals from Senegal were studied using multiparametric flow cytometry to investigate the frequencies and phenotypes of peripheral γδ T cells. γδ T-cell parameters and correlates of HIV disease progression were assessed. : We observed an expansion of Vδ1 T-cell populations in both HIV-1 and HIV-2 infection. However, unlike HIV-1 infection, no significant contraction of the frequency of total Vδ2 T cells was observed in HIV-2 infection. Significantly lower frequencies of CD4Vδ2 T cells were observed in HIV-2-infected individuals. Furthermore, frequencies of CD28CD45RO and CD27CD28CD45RO Vδ2 T cell were low in HIV-1-infected individuals. Vδ2 T-cell activation levels were elevated in both HIV-1-infected and HIV-2-infected individuals. The frequency of HLA-DRCD38-activated Vδ1 and Vδ2 T cells was associated with a decline in CD4 T-cell counts and increased viral load in both HIV-1 and HIV-2 infection. Although maintaining the normal frequency of total Vδ2 T cells, HIV-2 infection reduces the frequency of CD4Vδ2 T cells and alters the frequencies of subsets of Vδ1 T cells. Both HIV-1 and HIV-2 infection induce γδ T-cell activation, and this activation is associated with the disease progression.