The interaction between parathyroid hormone-related protein (PTHrP) and the parathyroid hormone (PTH)/PTHrP receptor is thought to play a role in the growth and differentiation of various tissues throughout fetal development in the rodent. The aim of the present study was to define the patterns of expression of PTHrP and of the PTH/PTHrP receptor in the rat uterus during the early stages of normal pregnancy, and following artificial induction of a decidual reaction. Using hybridization histochemistry, we have shown that the receptor gene is switched on early in pregnancy (by 1.5 days post coitum) in the endometrial stromal cells that surround the lumen. These cells include the anti-mesometrial subepithelial stromal cells that are destined to become decidualized. This pattern continues until 5.0 days post coitum, when PTHrP is switched on in antimesometrial luminal epithelial cells that line the implantation chamber. Stromal cells underlying the implantation chamber then downregulate transcription of the receptor gene, and within 12 h differentiate into decidual cells. A similar pattern was seen in uteri in which a decidual reaction had been induced artificially. Therefore, it may be postulated that in early pregnancy the endometrial stroma initiates transcription of the gene for the PTH/PTHrP receptor and is thus 'primed' for the PTHrP signal from the luminal epithelial cells. Some time after receiving the signal, the endometrial stromal cells downregulate the receptor gene, and this appears to be a trigger for the terminal differentiation of the stromal cells into decidual cells. These results suggest that PTHrP, acting through the PTH/PTHrP receptor, plays a role in the initiation of a decidual reaction during early pregnancy by regulating the differentiation of endometrial stromal cells into decidual cells.