Unilateral nephrectomy (UNX) is followed by a prompt functional adaptation (as well as initiation of compensatory growth) in the contralateral kidney. We assessed the possibility that dopamine (DA) receptor antagonism and angiotensin-converting enzyme inhibition may influence the acute natriuretic response to UNX of the remaining kidney in euvolemic anesthetized Sprague-Dawley rats with or without pretreatment by haloperidol or enalapril. Twenty to 80 min after UNX, urinary excretion of sodium and potassium approximately doubled and fractional excretion of lithium (an index of proximal tubular handling of sodium) increased by about one third in untreated rats, whereas glomerular filtration rate, renal plasma flow and mean arterial pressure (MAP) did not change significantly. Haloperidol infusion blunted the post-UNX increase in fractional excretion of lithium without affecting the natriuretic/kaliuretic response of the remaining kidney. Enalapril pretreatment resulted in lower MAP and marked renal vasodilation at baseline but no significant alteration in the response to UNX. These results indicate that the magnitude of post-UNX natriure-sis is not affected by suppression of angiotensin II (AH) generation or blockade of DA receptors. The lithium clearance data suggest that the immediate natriuretic response to UNX can be ascribed to both a proximal and a distal tubular phenomenon.