Vascular endothelial growth factor (VEGF) is a crucial regulator of angiogenesis that stimulates proliferation of endothelial cells and increases vascular permeability. Placenta growth factor (PlGF) is a member of the VEGF family that binds to VEGF receptor 1 (VEGFR-1) and can heterodimerize with VEGF. Its role in angiogenesis, however, is the subject of some debate. Teresa Odorisio and co-workers have examined the function of PlGF by generating transgenic mice that overexpress PlGF in the skin (seep. 2559). They find that the mice exhibit increases in the number, size and branching of blood vessels, as well as enhanced vascular permeability, which indicates that PlGF has a potent angiogenic effect. (The levels of homodimeric VEGF are reduced in keratinocytes from the transgenic mice probably owing to formation of VEGF-PlGF heterodimers.) Moreover, in contrast to mice overexpressing VEGF,mice overexpressing PlGF have strongly increased vessel sizes and hypervascularization persisting in adult life. The authors therefore conclude that the biological effects of PlGF are different from those of VEGF and do not simply reflect its postulated role as a decoy for its relative.