Overproduction of immunoglobulin E (IgE) and T helper cell type 2 (T H 2) cytokines, including interleukin 4 (IL-4), IL-5 and IL-13, can result in allergic disorders. Although it is known that IL-4 is critical to the polarization of naïve CD4+ T cells to a T H 2 phenotype, both in vitro and in many in vivo systems, other factors that regulate in vivo IL-4 production and T H 2 commitment are poorly understood. IL-18, an IL-1–like cytokine that requires cleavage with caspase-1 to become active, was found to increase IgE production in a CD4+ T cells−, IL-4–and STAT6–dependent fashion. IL-18 and T cell receptor–mediated stimulation could induce naïve CD4+ T cells to develop into IL-4–producing cells in vitro. Thus, caspase-1 and IL-18 may be critical in regulation of IgE production in vivo, providing a potential therapeutic target for allergic disorders.