Flt-3 Ligand, also known as FL, is an α-helical cytokine that promotes the differentiation of multiple hematopoietic cell lineages. Mature human Flt-3 Ligand consists of a 158 amino acid (aa) extracellular domain (ECD) with a cytokine-like domain and a juxtamembrane region, a 21 aa transmembrane segment, and a 30 aa cytoplasmic tail. Within the ECD, human Flt-3 Ligand shares 71% and 65% aa sequence identity with mouse and rat Flt-3 Ligand, respectively. Human and mouse Flt-3 Ligand show cross-species activity. Flt-3 Ligand is expressed as a non-covalently linked dimer by T cells and bone marrow and thymic fibroblasts. Each 36 kDa chain carries approximately 12 kDa of N- and O-linked carbohydrates. Alternate splicing and proteolytic cleavage of the transmembrane form can generate a soluble 30 kDa fragment that includes the cytokine domain. Alternate splicing of human Flt -3 Ligand also generates membraneassociated isoforms that contain either a truncated cytoplasmic tail or an 85 aa substitution following the cytokine domain. Both transmembrane and soluble Flt-3 Ligand signal through the tyrosine kinase receptor Flt3/ FlK-1. Flt-3 Ligand induces the expansion of monocytes and immature dendritic cells as well as early B cell lineage differentiation.