This genetic epidemiologic research on variants in key human immune response genes will help explain why individuals differ so widely in the ease with which they become infected with HIV and the rate at which they progress to disease. The knowledge is most directly relevant to the health of African populations. It will also translate into guidance for biomedical scientists who are grappling with the development of HIV vaccines and potential population differences in response to them, pursuing strategies for modulation molecules involved in viral entry into cells, and designing and analyzing intervention trials.