Expansion of a CD57+CD8+ T lymphocyte subset has been reported in HIV and human cytomegalovirus (HCMV) infection. Almost all of these T cells lack CD28 expression. While CD28– cells are often associated with anergy, some authors believe their expansion in HIV infection precipitates immunodeficiency. We studied 15 randomly chosen patients with immune activation and observed that CD57+CD28– T cell expansion may occur in various conditions and to the same degree as in HIV infection without resulting in immunodeficiency. Triple colour flow cytometry also revealed that the CD57 and CD28 antigens are coexpressed in only 3% of CD8+ T cells, irrespective of the underlying condition, so that almost all CD57+CD8+ cells are always CD28–. Analysis of Fas (CD95) expression with respect to CD28 expression on CD4+ and CD8+ T cells from 10 additional patients indicated no increased commitment to apoptosis in CD28– T cells. Semiquantitative polymerase chain reaction (PCR) comparing CD28+ and CD28–CD8+ T cells with respect to cytokine gene expression (tumour necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), IL-1β) in five renal transplant patients with expansion of the CD57+ subset detected no cytokine gene expression deficit in CD28– T cells. A direct association of increased proportions of CD57+CD28–CD8+ T cells with immunodeficiency/anergy is disputed.