The CD40 ligand (CD40L) is a member of the TNF family, and has emerged as a key molecule in the contact-mediated signal required for B cell activation and differentiation. The cloned CD40L expressed on heterologous cells, or in the form of soluble multimeric molecules, can directly activate B cells and, in conjunction with cytokines, can induce Ig isotype switching in naive B cells. Patients with hyper-IgM syndrome, which results from defective CD40L expression, generally have no circulating Ig, except for IgM, indicating that the CD40L is also important for Ig isotype switching, in vivo. CD40L does not play a role in B cell development and appears not to be required for human activation and differentiation. The presence of CD40L on cells other than T cells, the relatively broad distribution of its ligand CD40, and the ability of T cells to be co-stimulated via CD40L, indicates a broader role for CD40L-CD40 mediated intercellular communication.