PURPOSE OF REVIEW: The role of regulatory T cells (T) in peripheral tolerance has been studied extensively in transplantation research. Recently, mast cells have been shown to play an indispensable role in allograft tolerance. The purpose of this review is to inform the reader on the current standings of the role of mast cells in dominant tolerance with an emphasis on the interaction of mast cells with T. RECENT FINDINGS: Mast cells are required to sustain peripheral tolerance via T. T can stabilize mast cells degranulation by contact-dependent mechanisms through the interaction of OX40 and its ligand OX40L, and by production of soluble factors, such as interleukin-10 and transforming growth factor-β. Conversely, the activation and subsequent degranulation of mast cells break peripheral tolerance. SUMMARY: Both mast cells and T are needed to create a local immunosuppressive environment in the transplant. T are not only necessary to suppress effector T-cell responses but also to stabilize mast cells. Mast cells in return could contribute to the immunosuppressive state by release of transforming growth factor-β, interleukin-10 and specific proteases. However, the molecular basis for mast cells control of T suppression in organ transplantation is still unresolved.