This study was designed to compare the vascular reactivity intrinsic to uterine and femoral arterial smooth muscle from pregnant (0.92 term) and nonpregnant rabbits to angiotensin II (ANG II), norepinephrine (NE), and potassium chloride (KCl) using the isolated helical strip technique. Comparing dose-response relations, arteries from both groups were equally sensitive to NE and KCl. Uterine arteries from pregnant rabbits, however, exhibited a greater sensitivity to the vasoconstricting effects of ANG II (P less than 0.01). This selective increase in sensitivity to ANG II was not observed in femoral arteries. The altered ANG II response in uterine arteries from pregnant rabbits was unaffected by pretreatment with cocaine or phenoxybenzamine, thus ruling out an adrenergic mechanism mediating the response. In addition, evaluation of saralasin affinity (KB) for the uterine arterial ANG II receptor suggested that it was not altered in pregnancy. However, preincubation of uterine arteries from pregnant rabbits with meclofenamate or indomethacin consistently attenuated the ANG II response (P less than 0.05). Therefore, this study demonstrated that 1) uterine arteries from term pregnant rabbits show a selective and specific enhancement to ANG II vasoconstriction, and 2) this increased response of ANG II results from the local ANG II stimulation of synthesis of prostaglandins by the uterine arterial wall that have a net vasoconstricting action.