IMMUNOGLOBULIN E (IgE) is central to the induction of allergic diseases through its binding to the high-affinity receptor (FcɛRl) on mast cells and basophils. Crosslinking by allergens of the bound IgE leads to the release of various inflammatory mediators. IgE production by B cells requires a physical interaction with T cells¹, involving a number of surface adhesion molecules^1,2, as well as the soluble factors interleukin-4 (IL-4)^3,4 and IL-13 (ref. 5) produced by T cells^6,7, basophils⁸ and mast cells⁹. Here we report that, in the presence of IL-4, mast and basophilic cell lines can provide the cell contact signals that are required for IgE synthesis. The human cell lines HMC-1 (mast) and KU812 (basophilic) both express the ligand for CD40 (CD40L) which is shown to be responsible for the IgE production. Moreover, freshly isolated purified human lung mast cells and blood basophils are also shown to express CD40L and to induce IgE production. This evidence suggests that mast cells and basophils may therefore play a key role in allergy not only by producing inflammatory mediators, but also by directly regulating IgE production independently of T cells.