The effects of minoxidil and the angiotensin-converting enzyme inhibitor SQ 14,225 on blood pressure, sodium balance, plasma renin activity, plasma aldosterone concentration, aldosterone excretion rate, and renal function were studied in 11 drug-resistant hypertensive patients under controlled diets of sodium and potassium intake. Minoxidil treatment lowered blood pressure from 178/112 +/- 8/5 mm Hg (means +/- SEM) to 14/95 +/- 6/3 mm Hg. Plasma renin activity rose from 4.8 +/- 1.7 ng/ml/hr to 9.9 +/- 2.4; plasma aldosterone rose from 32.6 +/- 7.4 to 50.5 +/- 9.8 ng/dl; and aldosterone excretion rate rose from 7.6 +/- 1.3 to 15.2 +/- 3.5 micrograms/24 hr. Sodium retention could be controlled by increasing doses of diuretics, but a 10 mEq/day sodium intake in two patients resulted in significant increases of serum creatinine, and hyperkalemia was reversed by sodium loading. In five minoxidil-treated patients, substitution with the angiotensin-converting enzyme inhibitor SQ 14,225 lowered plasma and urinary aldosterone levels in two normal and high-renin patients but not significantly in three low-renin patients. Sodium excretion increased when aldosterone decreased, but blood pressure were more consistently controlled with minoxidil than with oral SQ 14,225.