Pulmonary hypertension has been described as a possible complication of the antihypertensive vasodilator, minoxidil. A prospective study was undertaken in seven severely hypertensive patients refractory to multiple drug therapy. Treatment was initiated with fixed doses of hydrochlorothiazide (100 mg/day) and propranolol (160 mg/day) for a control period. Mean systemic arterial pressure, cardiac output, and pulmonary artery pressure were then compared before and after the addition of acute (5 day) and chronic (2 month) therapy with minoxidil. Mean arterial blood pressure decreased from a control value of 135 mm Hg to a value of 104 mm Hg acutely and 108 mm Hg chronically. Significant increases in mean cardiac output occurred with minoxidil therapy (from 4.2 L/min control to 5.4 L/min acutely and 5.1 L/min chronically) despite concomitant propranolol treatment. Mean pulmonary artery pressure did not increase either acutely or chronically. The data suggest that in patients with normal pulmonary hemodynamics prior to treatment, pulmonary hypertension does not develop during two months of minoxidil therapy.