Placenta Growth Factor (PlGF) was recently discovered as a secreted growth factor for vascular endothelial cells and based on its homology to vascular endothelial growth factor (VEGF), can be classified as a new member of this growth factor family. We have carried out polymerase chain amplification (PCR) of RNA from human umbilical vein endothelial cells and placenta tissue and discovered a second species of PlGF, PlGF-2. PlGF-2 has a 21-amino acid insertion not present in PlGF-1 coding for a highly basic region near the C-terminus. This is similar to VEGF189. Northern analysis has shown, that the PlGF gene is expressed only in a limited number of cell types and tissues, e.g. human umbilical vein endothelial cells (HUVE) and placenta. Infection of Sf158 insect cells with recombinant baculoviruses specific for the two forms showed, that both, PlGF-1 and PlGF-2 are secreted efficiently into the supernatant and PlGF-2 can bind with high affinity to heparin. Both PlGF forms had a similar mitogenic potency for bovine aortic endothelial cells. Binding studies with 125I-VEGF165 demonstrate, that supernatant of PlGF expressing insect cells can compete for receptor binding. Similar to VEGF, PlGF can exist in different forms which are probably generated by differential splicing. The occurrence of two molecular forms of this endothelial specific growth factor suggests different physiological roles of the two forms during placental development and differentiation.