In the present study we have shown that the genetic expression of prostaglandin (PG)F_2α receptor (R) and cyclooxygenase (COX)-2 increases in laboring rat myometrium. This finding was associated with a relatively weak contractile in vitro response (E_max) of isolated uterine strips when challenged with PGF_2α. Five days postpartum PGF_2α-R mRNA values exceeded those during labor while COX-2 mRNA was reduced to preparturient values. Maximal contractility of isolated strips stimulated with PGF_2α at this time was enhanced and EC₅₀ decreased. Oxytocin treatment of estrogen-primed nonpregnant rats down-regulated uterine contractile responsiveness to PGF_2α, leaving mRNA values for this receptor unchanged, whereas oxytocin receptor blockade with atosiban (an oxytocin receptor antagonist) left E_max unaltered. In contrast, atosiban treatment of pregnant rats resulted in a 2.5-fold increase in E_max and a considerably reduced EC₅₀ during labor when compared to untreated delivering rats. The increased contractile ability was associated with a threefold increase in PGF_2α-R mRNA production, indicating that the regulation by atosiban of the PGF_2α-induced response is exerted at the genetic level. Based on the present data we suggest that 1) PGF_2α-R stimulation may not primarily exert a contracting role in the normally delivering myometrium, and 2) the presence of the PGF_2α-R system in rat myometrium may explain the apparent functional redundancy of the oxytocinergic system during the process of birth in animals lacking oxytocin or where the oxytocin receptor is blocked. In this context PGF_2α receptor stimulation may, in the absence of oxytocin receptor stimulation, exert the contractile forces needed for proper propulsion of the fetus.