A high prevalence of increased intima/media thickness of the arterial wall has been documented in hypertension. These alterations in vascular wall structure may be potent determinants for the promotion of the development of atherosclerosis. Direct histologic data from animal models of hypertension, and indirect data from hypertensive patients, have demonstrated a marked regression of increased intima/media thickness by angiotensinconverting enzyme (ACE) inhibition. Long-term effects of ACE inhibition on structural wall changes in humans have not been examined. Therefore, a multicenter, randomized, double-blind European trial was designed to compare the effects of the ACE inhibitor perindopril and the diuretic hydrochlorothiazide in slowing or reversing progression of increased intima/media thickness of carotid and femoral arteries in hypertensive patients. A total of 800 patients at 17 clinical centers in 7 European countries, aged 35–65 years, with hypertension and ultrasonographically proven intima/media thickness ≥0.8 mm of the common carotid artery will be randomly assigned to receive in a doubleblind fashion either perindopril or hydrochlorothiazide and will be followed for 24 months. High resolution duplex sonography will be used to quantify intima/media thickness at baseline and twice a year during follow-up. A change of 0.1 mm of intima/media thickness from baseline is considered to be detectable, and the standard deviations of the changes from baseline are expected not to be higher than 0.2 mm. The primary endpoint of the study is the comparison of changes in intima/media thickness of the common carotid artery. Secondary endpoints include comparison of the effectiveness of the two treatments on left ventricular mass, posterior wall thickness, intraventricular septal thickness, left ventricular end-diastolic diameter, and comparison of the 2 treatments on ultrasonographically determined thickness of the intima/media complex of the common femoral artery. Further analyses will assess the relation between intima/ media thickness changes and the changes of blood pressure, heart rate, low and high density lipoprotein cholesterol, triglycerides, and glucose. The study is designed to assess the impact of antihypertensive therapy on early pathological vascular wall changes and to clarify whether this is due to a drug-specific action or only dependent on the blood pressure lowering effect.