Regulatory T cells are considered to be pivotal for the induction of tolerance to donor antigens. In the past decades, several regulatory T-cell subsets have been identified, such as CD4(+)CD25(+) regulatory T cells and the CD8(+)CD28 suppressor T cells. Although many studies have investigated the rote of these regulators in transplant tolerance, relatively Little attention has focused on the exact place where these cells suppress immune responses directed to donor antigens. The localization of regulatory T cells may influence their effect on allogeneic immune responses. More insight into the localization and migration of regulatory T cells in transplant recipients is therefore important, especially when these cells are to be used for monitoring purposes and for cellular immune therapy. In the present review we summarize current knowledge about the presence of functional donor-directed regulatory T cells in the secondary lymphoid organs, peripheral blood, and the transplanted organ itself. In addition, we discuss the importance of the appropriate localization for the control of anti-donor immune reactivity. (C) 2008 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.