There are three signaling VEGF receptors. The VEGF family members PIGF and VEGF-B with exclusive binding capacities to the VEGFR-1 can influence monocyte activation and differentiation. The VEGFR-2 and VEGFR-3 binding VEGF homologues, VEGF-C and VEGF-D, are mitogens for both vascular and lymphatic endothelial cells. The orf virus encoded VEGF-E homologue binds and activates only the VEGFR-2 and thus may be the prototype of a vascular endothelial cell-specific growth factor. Further specific activities of VEGF and its homologues result from receptor-specific signaling and differential expression of ligands or receptors. A naturally occurring soluble form of the VEGFR-1 suggests a regulatory role for this receptor.