1. The effects of changes in the mean and amplitude of arterial wall shear stress on endothelium-dependent arterial dilatation of the iliac artery of the anaesthetized dog were examined. 2. Changes in the mean and amplitude of blood flow and wall shear stress were brought about by varying local peripheral resistance and stroke volume using a distal infusion of acetylcholine and the stimulation of the left ansa subclavia. Changes in the diameter of a segment of the iliac artery with the endothelium intact, relative to a segment with no endothelium, were used as an index of the release of nitric oxide. 3. The increase in mean blood flow was from 84 +/- 12 to 527 +/- 53 ml min-1 and in amplitude was from 365 +/- 18 to 695 +/- 38 ml min-1 (means +/- S.E.M.). The increase in mean wall shear stress was from 1.78 +/- 0.30 to 7.66 +/- 1.01 N m-2 and in amplitude was from 7.37 +/- 0.46 to 13.9 +/- 2.00 N m-2 (means +/- S.E.M.). 4. Increases in mean shear stress caused an increase in the diameter only of the section of artery with endothelium; the slope of the relationship was 0.064 +/- 0.006 mm N-1 m2 (mean +/- S.E.M., P < 0.001); changes in the amplitude of shear stress did not cause an increase in diameter. Changes in both the mean and amplitude of shear stress had no significant effect on the diameter of the section of artery with no endothelium. 5. These findings coupled with the known anti-atheroma effects of nitric oxide and the effect of shear stress on cell adhesion and platelet aggregation offer a possible explanation for the disposition of atheroma in those parts of the arterial system which have low mean and high amplitude of wall shear stress.