The role played by renal prostaglandin E<sub>2</sub> in the maintenance of hypertension in chronic renal disease has been investigated through studying the response of body weight, blood pressure, glomerular filtration rate (GFR), 24-hour natriuresis, plasma renin activity (PRA), plasma aldosterone and urinary PGE<sub>2</sub> excretion to the administration of indomethacin (2 mg/kg daily, during 3 days). A group of 37 patients diagnosed as having chronic renal parenchymatous disease with creatinine clearance above 25 ml/min was included in the study. 21 of them were hypertensive (BP > 160/95). 27 normotensive volunteers were also studied and considered as the control group. The initial study disclosed similar levels of PGE<sub>2</sub>, PRA and plasma aldosterone in volunteers, normotensive patients and hypertensive patients, although the sodium intake was lower in the last two groups. A positive correlation between PRA and urinary PGE<sub>2</sub> was found both in normotensive (r =0.507, p < 0.01) and in hypertensive patients (r =0.609, p < 0.01). The administration of indomethacin induced a diminution of PRA, plasma aldosterone and urinary PGE<sub>2</sub> levels together with an increase in diastolic blood pressure (p < 0.05–0.01) in both volunteers and patients. The remaining parameters measured did not change in volunteers or in normotensive patients. On the contrary, in hypertensive patients, during indomethacin administration, lower values of creatinine clearance (p < 0.005) and 24-hour natriuresis (p < 0.05) together with an increase in body weight (p < 0.0l) were observed. These results point to the existence of a protective role of renal prostaglandin E<sub>2</sub> upon renal function when hypertension appears in the course of chronic renal parenchymatous disease.