Interactions of vascular endothelial growth factor (VEGF) with its receptors VEGFR-1 and VEGFR-2 promoting angiogenesis have been described in placentation of human, mink and pig. The bovine placenta is multiplex, villous and synepitheliochorial due to migratory trophoblast giant cells (TGC). To determine the role of VEGF in bovine implantation and placentation, placentomes and interplacentomal areas from 33 cows from early implantation until near term were evaluated by immunohistochemistry. VEGF immunoreactivity was detected in fetal and maternal blood vessel tissues during implantation and throughout gestation, and in preimplantatory trophoblast cells and uterine epithelium. After implantation the immunoreaction was confined to TGC and uterine epithelium. An antibody against bovine VEGF revealed a strong reactivity in the stroma of maternal caruncular septa in early and mid-gestation, which distinctly decreased near term. In interplacentomal areas, VEGF was found in luminal and glandular epithelia as well as in trophoblast, with distinctly higher reactivity in giant cells. VEGFR-1 was observed in trophoblast and uterine epithelium around implantation. Later, in definite placentomes, VEGFR-1 was localized in TGC near the chorionic plate and in maternal endothelial cells in the center of the placentome. VEGFR-1 and VEGFR-2 were co-localized in uterine epithelium and trophoblast as well as in blood vessel tissue and uterine glands. The presence of VEGF, VEGFR-1 and VEGFR-2 at the feto-maternal interface and in vasculature indicates that in the bovine VEGF may have (1) classic functions in angiogenesis and vascular permeability, (2) growth factor properties, facilitating feto-maternal exchange via paracrine action, (3) chemotactic activity on capillary endothelium, and (4) an autocrine influence on TGC migratory activity.