To assess possible differences in immune status, proportions and absolute numbers of subsets of CD4+ and CD8+ T cells were compared between HIV− healthy Ethiopians (n = 52) and HIV− Dutch (n = 60). Both proportions and absolute numbers of naive CD4+ and CD8+ T cells were found to be significantly reduced in HIV− Ethiopians compared with HIV−Dutch subjects. Also, both proportions and absolute numbers of the effector CD8+ T cell population as well as the CD4+ CD45RA− CD27− and CD8+ CD45RA− CD27− T cell populations were increased in Ethiopians. Finally, both proportions and absolute numbers of CD4+ and CD8+ T cells expressing CD28 were significantly reduced in Ethiopians versus Dutch. In addition, the possible association between the described subsets and HIV status was studied by comparing the above 52 HIV− individuals with 32 HIV+ Ethiopians with CD4 counts > 200/μl and/or no AIDS-defining conditions and 39 HIV+ Ethiopians with CD4 counts < 200/μl or with AIDS-defining conditions. There was a gradual increase of activated CD4+ and CD8+ T cells, a decrease of CD8+ T cells expressing CD28 and a decrease of effector CD8+ T cells when moving from HIV− to AIDS. Furthermore, a decrease of naive CD8+ T cells and an increase of memory CD8+ T cells in AIDS patients were observed. These results suggest a generally and persistently activated immune system in HIV−Ethiopians. The potential consequences of this are discussed, in relation to HIV infection.