Human pregnancy is characterized by a blunted pressor responsiveness to vasopressor substances. This was first reported by Dieckmann and Michel in 1937 in experiments in which they measured vascular reactivity to the pressor effects of a crude preparation of vasopressin. Recently, this has been reported to occur in response to epinephrine, norepinephrine (NE), and angiotensin II (AII). Gant and associates reported that the increasing vascular sensitivity to infused AII not only was characteristic of women who developed pregnancy-induced hypertension, but in fact preceded the development of pregnancy-induced hypertension. Although a variety of factors may mediate this blunted pressor responsiveness, the most likely candidate appears to be the localized production within endothelium and/or vascular smooth muscle of prostaglandins. Indeed, administration of indomethacin or aspirin results in an increased sensitivity to infused AII in normotensive previously AII-refractory women. Administration of the steroid hormone 5 alpha-dihydroprogesterone reverses this apparent prostaglandin-mediated response. In addition, administration of the phosphodiesterase inhibitor, theophylline, results in a restoration of vascular refractoriness to infused AII in women with pregnancy-induced hypertension or in women destined to develop pregnancy-induced hypertension. Although a variety of known and possibly unknown compounds might also effect the control of vascular reactivity during human pregnancy, the prostinoids appear to play a pivotal role in mediation of control of vascular reactivity during human pregnancy.