CD40 ligand (CD40L) delivers a contact-dependent signal to B cells which, in the presence of interleukin (IL)-4, drives immunoglobulin isotype switching to IgE. CD40L expression in T cells is transient, requires activation of protein kinase C and a rise in intracellular calcium concentration ([Ca2+]i), and is inhibited by cyclosporin A (CsA). CsA also inhibited T-cell-dependent IL-4-driven IgE synthesis. We have found that expression of CD40L is developmentally regulated. Expression of CD40L was restricted to mature single-positive thymocytes which, in the presence of IL-4, were capable of inducing B cells to undergo IgE isotype switching. CD40L expression was severely decreased in cord blood lymphocytes and was associated with a severely decreased ability to undergo T-cell-dependent IgE isotype switching.