Mast cells play critical roles in hypersensitivity and in defense against certain parasites. We provide evidence that mouse mast cell survival and growth are promoted by monomeric IgE binding to its high-affinity receptor, FcϵRI. Monomeric IgE does not promote DNA synthesis but suppresses the apoptosis induced by growth factor deprivation. This antiapoptotic effect occurs in parallel with IgE-induced increases in FcϵRI surface expression but requires the continuous presence of IgE. This process does not involve the FasL/Fas death pathway or several Bcl-2 family proteins and induces a distinctly different signal than FcϵRI cross-linking. The ability of IgE to enhance mast cell survival and FcϵRI expression may contribute to amplified allergic reactions.