CD40 ligand (CD40L) is a membrane molecule that plays a key role in T cell-B cell cooperation, providing B cells the helper signals needed for activation, proliferation, differentiation and prevention of apoptosis. Patients with B-cell chronic lymphocytic leukemia (B-CLL) were studied to verify the following hypotheses: a) whether defective CD40L expression on activated T cells could account for deficient helper signals and therefore for hypogammaglobulinemia; b) whether aberrant CD40L expression on B cells could be a mechanism by which leukemic cells stimulate themselves via CD40 to escape apoptosis. Results showed physiological expression of CD40L on in vitro activated CD4+ cells, while this expression was absent on fresh and activated B cells. Abnormalities in CD40/CD40L interaction do not seem to play a role either in the pathogenesis of hypogammaglobulinemia or in lymphocyte accumulation in B-CLL.