Estrogen increases the α1-adrenergic contractile sensitivity of the rabbit uterus. Since estrogen treatment increases prostaglandin (Pg) production by the perfused rabbit uterus, and Pgs contribute to the ai-adrenergic contractile response, we postulated that estrogen’s effects on Pg production or response may play a role in the increased α1-adrenergic sensitivity induced by estrogen. We studied the effects of the eicosanoid synthesis inhibitor meclofenamate (60 μM) on the response to epinephrine (10-9-10-6 M) of uterine strips from ovariectomized, mature, and estrogen-treated rabbits in terms of both contractile response and Pge2 and Pgf2α production. We also measured the contractile response to Pge2 and Pgf2α (both 10-10-10-5 M) and Kc1 (70 M) of uterine strips from these groups. We found that in the ovariectomized rabbits, meclofenamate decreased Pg production, but did not alter the ar nergic sensitivity. In the mature rabbit uterus, meclofenamate decreased both Pge2 and Pgf2α production and reduced the aradrenergic sensitivity. In the estrogen-treated rabbit uterus, meclofenamate decreased Pgf2α, but not Pge2, production and did not alter the ai-adrenergic sensitivity. Finally, meclofena-mate reduced the contractile response to Kcl in all three groups, and exposure to Pge2 increased the contractile response to Kcl in both the mature and estrogen-treated rabbits. We conclude that Pgs play a role in the increase in the α1-adrenergic sensitivity of the uterus in mature rabbits, and that this may be the result of an estrogen-mediated alteration in the postreceptor effects of Pgs. © 1991 by The Endocrine Society.