We have characterized the dilation response to increased blood flow in the canine femoral and saphenous arteries. An arteriovenous shunt was created and changes in arterial diameter measured by sonomicrometer crystals. Increasing shunt flow approximately 10-fold caused a 9% increase in femoral and 15 % increase in saphenous artery diameter. The dilation response consisted of a transient decrease in diameter, followed by a rapid dilation and a slow return to control when flow was decreased. The increased diameter was not a result of decreased transmural pressure or alterations in pulse pressure. After removing the endothelial cells, the vessels did not dilate to increased flow or topical acetylcholine (10–5 M), but responses to norepinephrine (10–5 M) and sodium nitroprusside (10–4 M) were unaltered. Indomethacin, theophylline or propranolol did not affect the flow-induced dilation. Quinacrine, an inhibitor of phospholipase A2, attenuated the dilation response in a dose-dependent manner. We conclude that increased blood flow affects endothelial cells, causing an active dilation of arterial smooth m