In normotensive and hypertensive humans, prostaglandins, particularly PGE2 and PGI2, affect blood pressure through control of vascular resistance, salt excretion, cardiac output, and renin secretion. The majority of studies of human essential hypertension have documented diminished renal synthesis and, hence, urinary excretion of PGE2. The acute administration of indomethacin inhibits prostaglandin synthesis and increases total peripheral resistance as well as mean blood pressure, with a countervailing decrease of cardiac index. The important vasodilatory and natriuretic roles of PGE2 and PGI2 are most apparent in hypertensive patients receiving antihypertensive therapy. The concomitant use of NSAID attenuates blood-pressure control in all reported studies using indomethacin. Consequently, potent NSAID should be avoided during treatment of hypertensive patients, and aspirin may be the safest NSAID in these circumstances. Interesting data are accumulating on the beneficial effects of polyunsaturated fatty acids, particularly linoleic acid and eicosapentaenoic acid, as dietary means to reduce blood pressure. All reported studies have documented small 5 to 10 mm Hg decrements of blood pressure with dietary supplementation with these fatty acids and conversion of the ratio of polyunsaturated to saturated fatty acids toward unity.