Systemic and renal effects of the vasodilators dihydralazine and minoxidil were compared with those of the converting-enzyme inhibitor captopril (SQ 14225) and the AII antagonist sarisoleucin (Sar1Ile8-AII) in chronically sodium-depleted, two-kidney, two-clip hypertensive rats. Arterial blood pressure normalized in all experimental groups within 24 hours and remained normal until the end of the experiment. By day 4, plasma concentrations of creatinine and urea in animals treated by captopril or sarisoleucin were significantly higher than those measured after the administration of dihydralazine or minoxidil. Renal tubular lesions were also more frequently observed after the renin-angiotensin system (RAS) was blocked than they were after vasodilatation was induced by direct smooth muscle relaxation. Captopril and sarisoleucin stimulated the RAS more extensively than dihydralazine and minoxidil did. The results indicate that, in the presence of bilateral renal artery stenosis and sodium deprivation, systemic blood pressure normalization after the blockade of the RAS may be accompanied by acute renal failure. This may be explained partially by poststenotic renal hypotension, but it may also reflect a reduction of the GFR because of the blockade of intrarenal actions of AII.