Background: The liver efficiently eliminates activated CD8(+) T blasts. It is unknown if vaccine-primed CD8(+) T blasts migrate to and establish functional CD8(+) T cell immunity in the liver post-immunization. Aims: We tested, if functional CD8(+) T cell populations can be detected in the liver post-vaccination. Methods: Murine CD8(+) T cells with different epitope/restriction specificities were primed by intramuscular injection of protein- or DNA-based vaccines. The kinetics of appearance in the liver, as well as the surface phenotype and functional competence of intrahepatic, specific CD8+ T cell populations was tested. Results: High numbers of specific CD8(+) T cells appear in the liver after vaccination that are activated (CD69(+) CD44(+)), express effector functions (CD27(lo)/CD28(lo) phenotype, interferon gamma secretion, specific cytolytic reactivity), but show no evidence of apoptosis (annexin V-, B220(lo), similar numbers/kinetics in primed, congenic lpr/lpr mice). Specific CD8(+) T cells from the liver adoptively transferred into a naive, syngeneic host successfully reconstitute specific CD8(+) T cell immunity. Conclusions: Specific, functionally competent CD8(+) effector/memory T cell populations are established in the liver for months post-vaccination. (C) 2003 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.