Minoxidil-induced sequential changes in plasma renin activity, urinary aldosterone and norepinephrine excretion were assessed in 11 patients with severe hypertension receiving propranolol or oxprenolol, chlorthalidone and spironolactone. Blood pressure with this treatment alone averaged 175 +/- 7/114+/-4 mm Hg (mean +/- SEM). Addition of minoxidil in a dose of 5 to 35 mg/day (mean 16 mg/day) reduced blood pressure within one week to 125+/-5/87+/-3 mm Hg. Plasma renin, urinary aldosterone and norepinephrine increased two- to threefold initially, but returned to baseline within two weeks and remained unchanged during a mean follow-up of 6.8 months. In 6 patients beta-blocking drugs were then progressively reduced and withdrawn without adverse effects, though blood pressure and heart rate increased slightly in 5 patients who required readministration of minimal doses of beta-blockers. Neither renin nor urinary aldosterone or norepinephrine excretion changed significantly after discontinuation of beta-blockade. Thus, the stimulating effect of minoxidil on renin, aldosterone and norepinephrine secretion lasts less than 3 weeks. With long-term minoxidil treatment the need for beta-blockade is markedly reduced, and these drugs may even become unnecessary in some patients.