The flt-1 gene encodes for both the full-length receptor Flt-1 (VEGFR-1) and a soluble form designated sFlt-1. sFlt-1 carries the VEGF-binding domain of Flt-1 as well as a 31-amino-acid stretch derived from an intron and tightly binds VEGF, suppressing its angiogenic activity. The flt-1 gene has so far been identified only in mammals and is highly expressed in placenta as well as in vascular endothelial cells. In placenta, sFlt-1 is abundant in the trophoblast layer during pregnancy, suggesting that it is a negative regulator to excess angiogenesis and vascular permeability at the feto-maternal border in mammals. However, we show here for the first time that the flt-1 gene exists and is highly conserved in chickens. Surprisingly, the chicken flt-1 gene also encodes for sFlt-1 in addition to the full-length receptor. Similar to the mammalian sFlt-1, chicken sFlt-1 carries the VEGF-binding domain and a 31-amino-acid carboxyl region derived from an intron, which was significantly homologous to that in mammals. Chicken sFlt-1 is expressed early in embryogenesis. These findings strongly suggest that the natural antiangiogenic molecule sFlt-1 is widely conserved in vertebrates and regulates the angiogenic process. (C) 2002 Elsevier Science (USA).