Parathyroid hormone related protein (PTHrP) is an important humoral factor in hypercalcaemia of malignancy. In addition there is increasing evidence that this peptide has a physiological role in fetal development, especially in cellular growth and differentiation. Both in-situ hybridization and immunohistochemistry were used together and for the first time to identify sites of PTHrP gene expression and peptide in fetal and extra-embryonic tissues of first trimester human pregnancy. PTHrP mRNA and peptide were identified in the avascular amnion and the syncytiotrophoblast while mRNA alone was expressed in the cytotrophoblast. Its expression in these extra-embryonic tissues is consistent with postulated roles for PTHrP in implantation, relaxation of endometrial muscle and regulation of vascular tone. Expression of both mRNA and peptide occurred in endo-, mese- and ectodermal structures of the fetus, consistent with local production of the peptide rather than cellular uptake from amniotic fluid and supporting a role for PTHrP in cellular growth and differentiation.