Sensitivity to the vasoconstricting actions of adrenergic agents is altered during pregnancy and is drug-, regional vascular bed-, and endothelium-dependent. To examine whether the uterine perfusion-sparing property of ephedrine is due to local actions, we examined the effects in vitro of ephedrine and the alpha-adrenergic agonist metaraminol (10(-10)-10(-3) M) in uterine and femoral vessels, with and without functional endothelium, from nonpregnant and pregnant ewes. Both agents produced dose-dependent contractions in all vascular rings. In all cases metaraminol was more potent (by analysis of the concentration producing a 50% maximal response [EC50]) and efficacious (by maximal effect). Pregnancy increased constriction from both agents in femoral arterial rings, whereas pregnancy decreased constriction from both agents in uterine arterial rings. However, the ratio of maximal effect at femoral versus uterine rings during pregnancy was greater for ephedrine (5.2 +/- 0.6) than metaraminol (1.9 +/- 0.3). This difference was further accentuated by endothelium removal. Constriction to both agents was abolished by phentolamine (10(-5) M). These data suggest that both ephedrine and metaraminol constrict uterine and systemic vessels by actions on alpha adrenoceptors, and that ephedrine may spare uterine perfusion during pregnancy due to more selective constriction of systemic vessels than that caused by metaraminol.