The effects on renal sodium excretion of two systemic vasodilators, hydralazine and diazoxide, were investigated in volume expanded, anesthetized rats with unilaterally denervated kidneys. Urinary sodium excretion and fractional excretion of filtered sodium increased following hydralazine but decreased following diazoxide. Changes in renal hemodynamics were dissimilar as well: renal plasma flow was increased following hydralazine, but unchanged with diazoxide. All changes in renal sodium excretion and renal hemodynamics following hydralazine were prevented by pretreatment with indomethacin. Renal denervation accentuated the increases in fractional sodium excretion and renal blood flow that occurred following hydralazine. Hydralazine and diazoxide differ substantially in their effects on renal sodium excretion, apparently due to the stimulation of renal prostaglandins by the former agent. Although renal innervation attenuates the natriuretic effect of hydralazine, stimulation of the sympathetic nervous system does not account for differences in the renal effects of these two drugs.