In addition to being a major effector cell in the elicitation of allergic inflammation, mast cells have been found to be activated in various T cell–mediated inflammatory processes and to reside in close physical proximity to T cells. Such observations and the wide spectrum of mediators produced and secreted by mast cells have led investigators to propose a functional relationship between these 2 cell populations. Indeed, mast cell activation has been reported to induce T-cell migration either directly by the release of chemotactic factors, such as lymphotactin or IL-16, or indirectly by the induction of adhesion molecule expression on endothelial cells. Mast cells are also able to present antigens to T cells, resulting in their activation in either an MHC class I– or class II–restricted and costimulatory molecule-dependent fashion. Adhesion molecule–dependent intercellular contact or MHC class II cognate interactions between T cells and mast cells result in the release of both granule-associated mediators and cytokines from the latter. Also, T cell–derived mediators, such as β-chemokines, directly induce mast cell degranulation. On the other hand, mast cell–derived cytokines, such as IL-4, have been found to polarize T cells to preferentially differentiate into the T_H2 subset. Thus T cell-mast cell interactions are bidirectional, fulfilling regulatory and/or modulatory roles affecting various aspects of the immune response. (J Allergy Clin Immunol 1999;104:517-23.)