We compared the effects of sodium meclofenamate (5 mg/kg i.v.), an inhibitor of prostaglandin synthesis, on renal function in six unanesthetized dogs maintained for 5 to 7 days before the experiment on 100 mEq/day of NaCl and after sodium depletion by furosemide administration and salt deprivation. Plasma renin activity (PRA) during sodium depletion (12.35 +/- 3.93 ng ml-1 hr-1) was higher than during sodium repletion (1.46 +/- 0.47 ng ml-1 hr-1; P less than .05). The administration of meclofenamate did not alter mean arterial pressure, renal blood flow, urine volume, excretion of sodium and potassium or PRA in the sodium replete dog. However, during sodium depletion meclofenamate reduced renal blood flow from 168 +/- 35 to 105 +/- 23 ml/min (P less than .01) and urine flow from 0.32 +/- 0.09 to 0.16 +/- 0.05 ml/min (P less than .05) but did not affect mean arterial pressure, electrolyte excretion or PRA. The meclofenamate-induced reduction in renal blood flow during sodium depletion was well correlated with control PRA. After administration of meclofenamate, the urinary excretion of immunoreactive prostaglandin E2 fell by 66% (P less than .05) in the sodium replete dog and by 72% (P less than .05) in the sodium depleted dog. This study demonstrates that the effects of meclofenamate on renal hemodynamics vary with the state of sodium balance and in relation to PRA.