CD40 ligand (CD40L), a membrane protein expressed on activated T cells, plays a pivotal role in B cell proliferation and differentiation. Mutations in the CD40L gene are associated with a rare immunodeficiency state, X-linked hyper IgM syndrome (XLHIGM). Recently, platelets have been described as capable of expressing CD40L within minutes of stimulation. We have developed a rapid technique to determine expression of CD40L on activated platelets by flow cytometry in whole blood. We have demonstrated that this technique is useful in neonatal screening, in rapid diagnosis and in determining reconstitution by donor bone marrow post-transplantation.