Successful pregnancy depends upon placental growth and development, which follows a specific spatial and temporal sequence. Hepatocyte Growth Factor (HGF) is a potent mitogen, morphogen and motogen to both endothelial and epithelial cell types and is linked to a tyrosine kinase, proto-oncogene, c-met receptor. In 'normal' third trimester placentae (n = 5) full thickness biopsies (obtained at Caesarean section), immunolocalisation and in situ hybridisation studies were performed for HGF and c-met., respectively. HGF immunoreactive protein was present in mesenchymal core, the vaculosyncytial membrane (syncytotrophoblast) and the vascular endothelial cells of villous trophoblast. The HGF mRNA was present particularly strongly in the perivascular stromal cells surrounding the villous vasculature and the amnion/chorionic membranes. Immunoreactive c-met protein was strongly localised to the endothelial cells lining the villous vasculature and the vasculosyncytial membrane. A relatively weak and diffuse hybridisation signal for c-met mRNA was present throughout the villous trophoblast, most pronounced in the vasculosyncytial membrane. These results indicate that HGF may serve as a paracrine mediator to control placental development and growth.