One of the first cytokines described, MIF (macrophage migration inhibitory factor) was originally identified in studies of delayed hypersensitivity reactions where it was shown to inhibit macrophage migration. It is an important mediator of the innate immune response with potential roles in the pathophysiology of inflammatory, autoimmune, and neoplastic disorders. The human MIF gene encodes a 115 amino acid, 12.5 kDa secreted protein. Crystallographic studies suggest that MIF exists as a homotrimer, although some reports show that it may exist as a dimer or monomer as well. Although MIF exhibits no homology with other known cytokines, it shares structural homology with several bacterial enzymes. It has been speculated that MIF is an inflammatory mediator possibly associated with rheumatoid arthritis (RA) severity.