This study was designed to contribute to the understanding of the differences in the pathogenicity of HIV-1 and HIV-2 infection. The majority of HIV-2 infected patients show significantly slower development to disease than those with HIV-1 infection. Natural Killer (NK) cells are potent effectors of natural immunity and their activity could prevent human immunodeficiency virus type 1 (HIV-1) entry and replication in its target cells. We sought to determine whether NK cell immune responses are associated with the different clinical courses of HIV-1 and HIV-2 infections.