We tested the hypothesis that increased pulse wave reflection and altered backward waveform morphology contribute to increased pulse pressure in subjects with higher pulse pressure compared with lower pulse pressure and to actions of vasoactive drugs to increase pulse pressure. We examined the relationship of backward to forward wave morphology in 158 subjects who were evaluated for hypertension (including some normotensive subjects) divided into 3 groups by central pulse pressure: group 1, 33±6.5 mm Hg; group 2, 45±4.1 mm Hg; and group 3, 64±12.9 mm Hg (means±SD) and in healthy normotensive subjects during administration of inotropic and vasomotor drugs. Aortic pressure and flow in the aortic root were estimated by carotid tonometry and Doppler sonography, respectively. Morphology of the backward wave relative to the forward wave was similar in subjects in the lowest and highest tertiles of pulse pressure. Similar results were seen with the inotropic, vasopressor and vasodilator drugs, dobutamine, norepinephrine, and phentolamine, with the backward wave maintaining a constant ratio to the forward wave. However, nitroglycerin, a drug with a specific action to dilate muscular conduit arteries, reduced the amplitude of the backward wave relative to the forward wave from 0.26±0.018 at baseline to 0.19±0.019 during nitroglycerin 30 μg/min IV (P<0.01). These results are best explained by an approximately constant amount of reflection of the forward wave from the peripheral vasculature. The amount of reflection can be modified by dilation of peripheral muscular conduit arteries but contributes little to increased pulse pressure in hypertension.