Three cell membrane receptor tyrosine kinases, Flt-1 (also designated VEGF-R1), Flk-1 (also designated VEGF-R2) and Flt-4, putatively involved in the growth of endothelial cells, are characterized by the presence of seven immunoglobulin-like sequences in their extracellular domain. These receptors exhibit high degrees of sequence relatedness to each other as well as lesser degrees of relatedness to the class III receptors including CSF-1/Fms, PDGR, SLFR/Kit and Flt-3/Flk-2. Two members of this receptor class, Flt-1 and Flk-1, have been shown to represent high affinity receptors for vascular endothelial growth factors (VEGFs). On the basis of structural similarity to Flt-1 and Flk-1, it has been speculated that Flt-4 might represent a third receptor for either VEGF or a VEGF-related ligand.