The remodelling of the maternal uterine spiral arteries during pregnancy, known as physiological change, is critical for the normal growth and development of the fetus. Controversy has surrounded the part played by fetal trophoblast in the transformation of these spiral arteries. To address this debate, a histological and immunochemical comparison of blood vessels from the implantation sites of human pregnancies of early gestation with uterine tissue where trophoblast was absent was performed. Results showed that true physiological change, with the features of medial necrosis and deposition of fibrinoid material, only occurred in the presence of trophoblast. In addition, it was found that subpopulations of trophoblast contribute differently in the process. Interstitial trophoblast-mediated destruction of the arterial media precedes replacement of the endothelial cells by endovascular trophoblast.