Saralasin, an angiotensin antagonist, was used to study the role of renin-angiotensin in the vasodilator-beta-blocker drug interaction in hypertensive subjects. Plasma renin activity was elevated by withdrawal of propranolol in seven patients using minoxidil and propranolol. After propranolol withdrawal, saralasin caused hypotension (100/60 mm Hg or less) in five. Propranolol lowered blood pressure and plasma renin activity and diminished the hypotensive response to saralasin. Saralasin induced renin release in all patients, an effect blocked by propranolol. We conclude that angiotensin can be the major determinant of blood pressure in vasodilator-drug treated patients, that propranolol lowering of blood pressure in this vasodilator-beta-blocker drug interaction is related to suppression of renin release, and that the angiotensin feed-back-suppression mechanism for inhibiting renin release in functionally located proximal to beta-adrenergic receptors mediating renin release.