Nitroglycerin (NTG) reduces aortic pressure augmentation (AP) and index (AIx), by a mechanism thought to involve a reduction in pressure wave reflection by selective dilation of muscular arteries. We examined this assumption by comparing effects of NTG with those of phentolamine (PHT) a vasodilator with little action on muscular arteries. Seven healthy subjects aged 35–62 were studied receiving PHT (1.12, 2.25 and 4.5 mg bolus/infusion i.v.) and NTG (90, 300, 900 μg i.v. infusion over 30 min) on separate occasions in a cross-over study. Central pressures (from radial tonometry) and carotid-femoral pulse wave velocity (cfPWV) were assessed using the SphygmoCor system. Brachial, carotid and abdominal aortic diameter were recorded by ultrasound. NTG (90 μg) reduced AIx from 22.2±5.5 to 13.7±5.7% (P<0.05) and PHT (4.5 mg) produced a similar reduction from 24.6±5.1 to 15.6±5.7% (P <0.05). These changes in AIx were observed in the absence of any significant fall in mean arterial blood pressure (MAP) or cfPWV. NTG (90 μg μg/min) produced a greater dilation of the brachial artery than of the carotid or aorta and vasodilation of the brachial artery by this dose of NTG was significantly greater than that by PHT (4.5 mg): 11±0.19 vs. 2.6±0.13% (P<0.01). These results suggest that, although actions of NTG are associated with dilation of muscular arteries, this is not necessarily the action leading to a reduction in AIx. Actions on other parts of the vascular tree and/or on ventricular ejection may be responsible for the reduction in AIx by NTG and PHT.