Changes in the migration pattern of lymphocytes represent a key event in the evolution of an immune response since they enable lymphocytes to gain access to infected tissues. We studied the location of virus-specific CD8 T cells in various splenic compartments in response to infection with lymphocytic choriomeningitis virus (LCMV), either in situ or by adoptive cell transfers using T cells from transgenic (tg) mice expressing an LCMV-specific TCR. Naive tg T cells were predominantly localized in the periarteriolar lymphoid sheath, where they proliferated extensively after virus infection. In contrast, in vivo activated effector T cells failed to enter white pulp areas and accumulated in the red pulp. The different homing patterns of naive and effector CD8 T cells in vivo correlated well with their CCR7 chemokine receptor expression and their reactivity to the secondary lymphoid tissue chemokine (SLC). Thus, down-regulation of CCR7 expression on CD8 effector T cells rendered them unre sponsive to SLC, which controls T cell homing into white pulp of spleen and lymph nodes. Exclusion of CD8 effector T cells from these sites may represent an important mechanism to protect professional antigen-presenting cells from cytotoxic T cell attack and thus to prevent a prematuredecline of the immune response.