Interleukin-16 was first described in 1982, by Center and Cruikshank, as a lymphocyte chemoattractant factor generated from mitogen-stimulated human peripheral blood mononuclear cells [1,2]. The original name for IL-16 was lymphocyte chemoattractant factor (LCF), given that designation because of its first described function of the induction of T lymphocyte migration. Since that initial observation the structure, mechanism of action and other biological functions have been more fully elucidated, and much of that work will be outlined in this review. In lymphocytes, IL-16 is generated as a precursor molecule which is enzymatically cleaved following stimulation with T cell mitogens resulting in the secretion of a 17kDa peptide [3]. This peptide consists of approximately 130 amino acids and originates from the carboxyl terminal of the promolecule. All the identified bioactivity is contained within the secreted peptide, however, bioactivity is observed only following autoaggregation of the peptide into what are believed to be homodimers. It is uncertain at present whether IL-16 aggregation occurs within the cell prior to secretion, or occurs following secretion. Limited aggregation of monomeric peptides into the tetrameric form is observed under physiological conditions in vitro. HPLC analysis of native IL-16 from stimulated human T cells and recombinant IL-16 protein generated in COS cells or Escherichia coli has demonstrated that bothpreparations exist predominantly (>80%) in multimeric form [4]. The predicted amino acid sequence of secreted IL-16 contains six β sheets. Contained within the second β sheet is a PDZ domain as indicated by the amino acid sequence G-L-G-F. This sequence has been associated with protein-protein interactions [5] and may facilitate IL-16 monomer aggregation.