Large artery properties constitute an important component of left ventricular afterload in hypertension. The present study examined whether such properties were particularly responsive to angiotensin converting enzyme inhibitor therapy. A prospective, randomized, 12-week study in 138 previously treated hypertensive subjects, in 67 of whom usual treatment (UC) was replaced with perindopril (P) therapy. Large artery properties were assessed as central arterial pressure augmentation determined by applanation tonometry of the radial artery and a transfer function. At baseline both augmentation index (AI, %) and pressure (AP, mm Hg) were related to body size, heart rate, and gender. In addition AP was related to age and systolic blood pressure (BP). After 12 weeks of treatment AP decreased significantly in both perindopril and UC groups, whereas AI only decreased significantly (151.7%+/-2.3% to 144.9%+/-2.6%) in those treated with perindopril. Decreases in AP (-4.2+/-0.9 mm Hg v -1.9+/-0.7 mm Hg) and AI (-6.8%+/-2.2% v -2.2%+/-2.5%) from week 0 to week 12 were greater in the perindopril-treated group, but differences between groups failed to reach statistical significance (P = .05 and .09, respectively). The change in AI during the 12-week treatment period was dependent on the initial heart rate (P < .001), systolic BP (P < .05), weight (P < .001), and sex (P < .001), but not on treatment group (P > .5). Al at 12 weeks was negatively correlated with heart rate but regression slopes for the association were virtually identical for perindopril and UC groups. Perindopril treatment produces a greater decrease in AI than continuation with previous therapy, but this can be largely explained by hemodynamic changes rather than direct arterial effects.