The role of the renin-angiotensin system in the adaptation of late steps in aldosterone biosynthesis to sodium intake was studied in potassium-deficient rats. Capsular portions of adrenal glands were incubated with [3H]corticosterone and conversion to aldosterone and 18-hydroxycorticosterone was measured by double isotope dilution and multiple paper chromatography. Sodium loading of sodium- and potassium-depleted rats resulted in a rapid and extensive fall in PRA but only in a delayed and gradual suppression of aldosterone biosynthesis. Treatment with the converting enzyme inhibitor, captopril, did not affect aldosterone biosynthesis in rats with established sodium and potassium deficiency, but blocked the stimulation of the conversion of corticosterone to aldosterone and 18-hydroxycorticosterone by sodium restriction of potassium-depleted rats. Infusion of a high dose of angiotensin II into potassium-deficient rats stimulated aldosterone biosynthesis depending upon the concurrent sodium intake. Accordingly, the renin-angiotensin system plays an important but limited role in the control of late steps of aldosterone biosynthesis by sodium intake. Angiotensin II seems to be essential for the induction but not for the maintenance of a high activity of the enzyme(s) involved in the conversion of corticosterone to aldosterone during combined sodium and potassium restriction. The sensitivity of the zona glomerulosa to the long term stimulatory action of angiotensin II varies with the sodium intake and appears to be regulated by the plasma potassium concentration and unknown other mediators.