Prostaglandins (PGs) interact with specific receptors on plasma membranes to regulate myometrial activity in many species. The present study examined whether the expression of relaxant prostaglandin E receptor subtype two (EP₂) and contractile prostaglandin F receptor (FP) mRNA in the rat uterus is changed during various states of pregnancy and regulated by steroid hormones. Expression of mRNA for EP₂ and FP receptors in the full-thickness uteri was analyzed by reverse transcription-polymerase chain reaction using specific primers. Abundance of receptor mRNA was expressed relative to β-actin mRNA. Results showed that 1) mRNA for EP₂ receptors in the rat uterus was substantially increased during pregnancy (320%) compared with the nonpregnant state (100%, P < 0.01), and declined during labor at term (36% vs. 100% in control, P < 0.01); 2) mRNA expression for FP receptors in rat uterus was increased during pregnancy (333% vs. 100% in nonpregnant rats, P < 0.01) and reached maximal levels during labor (515% vs. 100% in control, P < 0.01); 3) upon RU-486 treatment on Day 19 of pregnancy, uterine EP₂ receptor mRNA levels were decreased (18% vs. 100% in control, P < 0.01), and FP mRNA levels were increased (357% vs. 100% in control, P < 0.01); 4) with ICI 164384 (an antiestrogen) treatment on Day 19 of gestation, uterine FP receptor mRNA levels were decreased without effects on EP₂ receptors; 5) in ovariectomized (ovx) rats, progesterone increased EP₂ (163% vs. 100% in control, P < 0.01) and had no effects on FP receptor mRNA expression in the rat uterus; 6) estradiol increased FP receptor mRNA levels (358% vs. 100% in control, P < 0.01) and had no effects on EP₂ mRNA in the ovx rat uterus. Therefore, we conclude that steroid hormones modulate the mRNA for relaxant EP₂ and contractile FP receptors for PGs in the uterus and thus regulate uterine activity during pregnancy and labor.