VEGFD was most closely related to VEGFC by virtue of the presence of N- and C-terminal extensions that were not found in other VEGF family members. In adult human tissues, VEGFD mRNA was most abundant in heart, lung, skeletal muscle, colon, and small intestine. Analyses of VEGFD receptor specificity revealed that VEGFD is a ligand for both VEGF receptors: VEGFR2 (FLK1) and VEGFR3 (FLT4); furthermore, VEGFD activates these receptors. However, VEGFD did not bind to VEGFR1. Expression of a truncated derivative of VEGFD demonstrated that the receptor-binding capacities reside in the portion of the molecule that is most closely related in primary structure to other VEGF family members and that corresponds to the mature form of VEGFC.