Several pressor factors were studied before and during chronic minoxidil therapy (median dose 27.5 mg/day) in 16 patients with hypertension that was refractory to conventional drugs. Following treatment with minoxidil and intensified diuretic therapy, blood pressure was decreased markedly; pulse rate, body weight, plasma volume, plasma aldosterone and epinephrine levels were not significantly altered, while plasma renin activity tended to be increased. Supine and upright plasma norepinephrine concentrations were increased by 140 (P less than 0.005) and 50% (P less than 0.05), respectively, but no significant change in urinary norepinephrine excretion was apparent. The latter parameter may not be a close index of sympathetic activity in patients with severe hypertension treated with minoxidil. While a search for underlying pheochromocytoma is always indicated in refractory hypertension, it appears mandatory to evaluate plasma catecholamines prior to or following discontinuation of treatment with minoxidil, to avoid a wrong diagnosis of pheochromocytoma.