The T cell repertoire required to control acute and latent CMV infection in otherwise healthy individuals was examined using both functional analysis and a wide range of MHC I tetramers. Both frequency and function of CMV specific T cells varied considerably between subjects, however, within subjects values remained stable over time. In total 16 +/- 3.5 CMV specific T cells/mul blood was detected, with obvious immunodominance between different CMV epitopes. Most subjects with latent infection showed low CMV specific T cell activity, whereas a subgroup (1/3) of individuals was high in either frequency or function of their CMV specific T cells. Patients with acute infection displayed high initial, but rapidly decreasing, numbers of CMV specific cells. In conclusion, a majority of healthy individuals readily seem to control latent CMV infection, whereas a subpopulation (1/3) of individuals uses a large proportion of their CD8+ T cell repertoire to control the infection.