Hybridization histochemistry and solution hybridization studies were performed to localize the expression of parathyroid hormone-related protein (PTHrP) during implantation in rats. Parallel studies were performed on rat uteri bearing oil-induced deciduomata and on cultured blastocysts. PTHrP mRNA begins to be expressed at day 5.5 of gestation by the uterine epithelium in the anti-mesometrial crypts marking the sites of implantation and in comparable regions during induction of deciduoma. Trophoblastic giant cells express the gene as soon as they are phenotypically recognizable both in vivo and in culture, but PTHrP mRNA cannot be detected in the early blastocyst or in cells of the inner cell mass. Decidual cells produce PTHrP mRNA both in normal gestation and after the induction of deciduomata. In each case, the expression of the gene in decidual cells follows its expression in uterine epithelium by 48 h. The uterine topographical location and time of expression of the PTHrP gene suggests that it plays a part in the implantation of the blastocyst.