In a double-blind cross-over study, the arterial changes produced by hydrochlorothiazide were compared with those observed after the calcium antagonist felodipine in 16 patients with mild to moderate systemic hypertension. Diameter changes at the site of the common carotid and brachial arteries were investigated using pulsed Doppler velocimetry, and pulse-wave velocities of the aortic, brachial and femorotibial areas were measured using standard noninvasive techniques. Whereas hydrochlorothiazide and felodipine similarly decreased blood pressure, hydrochlorothiazide did not change pulse-wave velocity, and the diameters of the brachial and common carotid arteries. Felodipine significantly decreased pulse-wave velocity, and increased brachial arterial diameter and compliance, with no change in carotid arterial diameter. Evidence was found that although felodipine had specific effects on the arterial system of hypertensive subjects, hydrochlorothiazide did not produce any sizable arterial change. These differential effects may influence specifically the heart afterload, with important consequences for diuretics that are known to cause minimal changes in cardiac structure and function.