The role played by renal prostaglandins E<sub>2</sub> (PGE<sub>2</sub>) and F<sub>2α</sub>(PGF<sub>2α</sub>) in the modification of sodium homeostasis in chronic renal failure (CFR) was studied. The 24-hour urinary excretion of PGE<sub>2</sub> and PGF<sub>2α</sub> was measured before and after 5 days of a diet containing less than 20 mmol/day of sodium in 6 patients with CRF. At the end of this period, an acute sodium load (77 mmol/h of NaCl for 4 h) was administered and prostaglandins measured in hourly urine collections. In contrast to the findings previously reported in normal subjects, PGE<sub>2</sub> and PGF<sub>2α </sub>decreased with the low-sodium diet. The ratio PGE<sub>2</sub> / PGF<sub>2α</sub> (reflecting the activity of the enzyme PGE<sub>2–</sub>9-ketoreductase) was greatly increased and did not change with the low-sodium diet. The acute sodium load induced an increase in urinary prostaglandins. The results suggest that prostaglandins may contribute to natriuresis in CRF, under basal conditions, after a short-term sodium depletion and in response to an acute sodium load. The changes in prostaglandin excretion in CRF could be related to decreased activity of PGE<sub>2–</sub>9-ketoreductase.