The full development of allergic airway responses in asthma is critically dependent on CD4+ T cells. Through interaction with CD4 molecule, IL-16 acts specifically on CD4+ cells. In vitro, IL-16 has been characterized as a chemoattractant for CD4+ immune cells and as a regulator of T cell functions inhibiting T cell receptor-mediated activation, an effect that is more predominant in T 2 cells. IL-16/CD4 interaction also regulates chemokine receptor signaling. The contribution of IL-16 in allergic airway inflammation has been studied both in humans and in animal models of asthma. Airway expression of IL-16 is upregulated in patients with ongoing asthma and in experimental models of allergic airway inflammation. The immunomodulatory function of IL-16 has been demonstrated in murine models of asthma in which systemic treatment with IL-16 inhibits antigen-induced airway responses and T 2 T cell cytokine production. This review addresses the current data regarding IL-16 protein and gene structure; the interaction of IL-16 with CD4; the biological activities of IL-16; its immunoregulatory role in allergic airway inflammation. In addition, we discuss the known and potential therapeutic applications for IL-16 and IL-16 peptide derivatives in allergic airway inflammation.