To clarify the role of renal prostanoid in hyperreninemia and high blood pressure in human renovascular hypertension, we measured prostaglandin E2 and renin activity in renal venous and abdominal aortic plasma before and after the intravenous administration of the cyclooxygenase inhibitor, aspirin DL-lysine. Subjects were six patients with unilateral renovascular hypertension and six with essential hypertension. In patients with renovascular hypertension, prostaglandin E2 concentration in renal venous plasma from the stenotic kidney was 9.25 +/- 1.48 pg/ml, which was significantly higher (p less than 0.01) than the concentration in the renal venous plasma from the normal kidney (4.97 +/- 1.02 pg/ml) or in the aortic plasma (2.59 +/- 0.15 pg/ml). Plasma renin activity was also higher in the renal vein of the stenotic kidney than in the other two sites. The stenotic side/normal side ratio of the renal venous prostaglandin E2 correlated significantly with a renin ratio greater than 1.5 (r = 0.8211, p less than 0.05). Intravenous injection of aspirin DL-lysine (18 mg/kg) 30 minutes later markedly suppressed prostaglandin E2 and renin levels at all sites and clearly lowered arterial blood pressure (mean: from 120 +/- 6 to 110 +/- 5 mm Hg, p less than 0.01). The reduction in blood pressure correlated significantly with the suppression of plasma renin activity in the aorta (p less than 0.05) and in the renal vein of the stenotic kidney (p less than 0.01). Conversely, in patients with essential hypertension, aspirin had little effect on renin levels and increased mean blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)