The aim of this study was to provide a basis for investigating the effects of one very common environmental factor, Epstein-Barr virus (EBV), on age-related changes in the immune system. To this end, the frequency of CD8(+) T cells carrying receptors for an immunodominant EBV lytic epitope was assessed by direct staining with HLA-peptide tetrameric complexes in 19 very old (>87 years) and 12 young (20-40 years) EBV carriers. The frequency of EBV-tetramer-positive cells within the CD8(+) subset was significantly greater in the old compared to the young group (P=0.001). However, the frequency of EBV antigen-specific IFN-gamma producing T cells, as determined by ELISPOT, was significantly lower in the old (P=0.001). Therefore, the absolute number of functional EBV-specific T cells in the elderly and the young was probably similar. These data suggest CD8 clonal expansions in the elderly, resulting in an accumulation of dysfunctional EBV-specific cells which possibly fill the 'immunological space' and could lead to a shrinking of the T cell repertoire for other novel antigens. This may help to explain the increased incidence and case-fatality caused by viruses and intracellular pathogens in the elderly.