It is now well established that human mast cells (MCs) are a source of several multifunctional cytokines. Preformed immunoreactive tumor necrosis factor-α (TNF-α) has been observed within human skin, and pulmonary MC granules are released after IgE-dependent activation. Recent studies in animal models indicate that mouse MCs may play a protective role in host defense against bacteria through production of TNF-α, mainly as a result of Tolllike receptor 4 (TLR4)- or CD48-mediated activation. Moreover, several recent observations in animal models have indicated that MCs may also play a pivotal role in coordinating the early phases of autoimmune diseases through production of TNF-α, particularly as a result of FcγRIII-mediated activation by autoantibodies. The questions now concern how MCs modulate immune responses and what cytokines MCs release through activation of each receptor. Since we recently identified functional TLR4 and FcγRI on human MCs, in this study we used high-density oligonucleotide probe arrays (GeneChip) to compare each of the receptormediated gene expression profiles with the FcεRI-mediated gene expression profile. The results indicated that human MCs might modulate the immune system in a receptor-specific manner by releasing cytokines in quantitatively and qualitatively different ways.