SUMMARY The role of renin-angiotensin system has been examined in the maintenance of hypertension in acute and chronic two-kidney (36 weeks) and chronic one-kidney (12 weeks) Goldblatt hypertensive rats using three inhibitors of this system. The inhibitors used were URI-73A, a synthetic analog of lysopbosphatidylethanolamine, which inhibits renin both in vivo and in vitro, SQ14.225, a potent conrerting enzyme inhibitor, and [Sar1, Thr*] angiotensin II, an angiotensin II antagonist. When the inhibitors were administered in acute (high renin) hypertensive rats, they all lowered blood pressure significantly. However, in the chronic (low renin) hypertensive phase, both renin and converting enzyme inhibitors lowered blood pressure, whereas, Sar', Thr* failed to lower Mood pressure. The renin inhibitor lowered plasma renin activity (PRA), and SQ 14,225 and [Sar1, Thr*] Ang II increased PRA. Further studies on water and electrolyte balance with one-kidney model hypertensive and uninephrectomized control rats showed no change in plasma volume. However, there was increased 24-bour urinary output and increased sodium excretion. This study indicates that in chronic renal hypertensive rats, blood pressure reduction is possible by either renin or converting enzyme inhibitor, but not by angiotensin antagonists. Since volume did not change either during the development or reversal of hypertension, volume did not appear to play a major role in the maintenance of hypertension.