Interleukin-16 (IL-16) is a pro-inflammatory cytokine. It is synthesized as a precursor molecule that is processed by cleavage of a C-terminal 14 kDa peptide, which aggregates into bioactive tetramers. IL-16 requires the expression of CD4 for its functions, which include induction of chemotaxis, interleukin-2 receptor and HLA-DR expression, reversible inhibition of TcR/CD3-dependent activation and induction of a repressor of HIV-1 transcription. It represents a major source of the lymphocyte chemotactic activity early after antigen challenge of atopic asthmatics in which the major cell of origin is the epithelium, although mast cells, CD8 cells, CD4 cells and eosinophils are also sources; and the presence of IL-16 directly correlates with the number of infiltrating CD4+ T cells. Potential therapeutic applications are use of inhibitors of IL-16 in asthma and for IL-16 in selective CD4+ T cell immune reconstitution in HIV-1 infection or following chemotherapy.