1. Although arterial blood flow is recognized as an important modulator of vascular tone and geometry, the effect of acute changes in shear-stress on conduit artery mechanics has not been fully investigated in humans because of technical limitations. 2. To assess, respectively, the effects of decreases and increases in flow and shear stress on radial artery tone and mechanics, arterial pressure (photoplethysmography), total blood viscosity, radial artery internal diameter, wall thickness (echotracking) and blood flow (Doppler) were measured in healthy volunteers (mean (+/-SEM) age 25 +/- 1 years) during a distal flow arrest (n=12) and hand skin heating (n=18). 3. Radial artery flow decreased from 31 +/- 4 to 7 +/- 1 10(-3) L/min during distal flow arrest (P < 0.001) and increased from 10 +/- 2 to 22 +/- 4 and 69 +/- 6 10(-3) L/min during heating (P < 0.001). At mean arterial pressure, these changes in flow were respectively associated with a parallel flow-dependent reduction and increase in diameter and midwall stress. There was no significant modification in mean elastic modulus. Compliance did not change when flow decreased and only increased at the highest level of flow. Finally, the cross-sectional compliance and incremental modulus were fitted as functions of midwall stress. The decrease in flow was associated with an upward shift of the modulus-midwall stress curve and a downward shift of the compliance-midwall stress curve. The increase in flow was associated with a downward shift of the modulus-midwall stress curve and an upward shift of the compliance-midwall stress curve at each level of wall shear stress. 4. By using two different procedures, we obtained similar results concerning the direct effects of increases and decreases in flow on stiffness of the arterial wall and on arterial compliance and demonstrated the presence of a flow-dependent regulation of arterial smooth muscle tone of peripheral conduit arteries in humans.