The purpose of this paper is to characterize the vasomotor properties of collateral vessels and summarize knowledge of the impact of exercise training/physical activity (EX) on these properties. The focus is on vasomotor properties of collateral vessels that provide blood flow to cardiac and skeletal muscle because this is my experience. Vasomotor Properties of Collaterals: In response to occlusive vascular disease inadequate blood flow is provided downstream of the occlusion which chronically stimulates a number of adaptations that help restore blood flow toward normal. Structural enlargement of collateral vessels is well characterized in animal models (Laughlin et al. 2012). There is relatively less appreciation of the importance of vasomotor reactivity of collateral vessels but it is known that vasomotor properties of collateral arteries differ from those of normal arteries. Compared to normal arteries, the constrictor response to ET-1, U46619, KCl, thromboxane A2, are reported to be blunted in collateral arteries (Angus et al.1991). Dilator responses to adenosine SNP and cromakalin are normal or increased in collaterals. In contrast, endothelium-dependent dilation (EDD) is generally reported to be blunted in peripheral collateral arteries (Taylor et al. 2008) and collateral dependent coronary arteries and arterioles (Griffin et al. 1999 & 2001). Peripheral collateral arteries exhibit unaltered constrictor responses to phenylephrine (Taylor et al. 2008). It is possible that these EDD is blunted due to decreased intravascular pressure downstream of arterial occlusion (EDD is blunted when normal arteries are evaluated at the low pressures comparable to those reported in collateral vessels.) On the other hand, the low luminal pressure caused by upstream obstruction also modifies flow distribution to enhance blood flow through the collateral circuit in a nitric oxide (NO)-dependent manner. When exercise is imposed on the collateral circuit, it may result in an increased shear stress and thereby contribute to the enlargement of, and increased EDD of, the collateral vessels. Flow-induced dilation, an EDD response, is blunted in collateral arteries. Indeed, peripheral collateral arteries exhibit a modest dilation at low shear stress and then a significant vasoconstriction with increasing shear stress whereas similarly sized arteries simply demonstrate dilation. Colleran et al (2010) suggested this may be the result of an interaction of NO with reactive oxygen species (ROS) producing peroxynitrite which stimulates vasoconstriction via thromboxane A2 production through the COX pathway. Effects of exercise training: Several investigators have tested the hypothesis that, since shear stress is increased during exercise (due to the increased blood flow), chronic EX would stimulate adaptations in vasomotor control of collateral vessels including an enhanced EDD (Laughlin et al. 2012). In addition, it appears that EX can modify the responses of vascular smooth muscle in collateral arteries as evidenced by an EX-induced reversal of the modest reduction in vasodilator responsiveness to sodium nitroprusside (Colleran et al. 2010). Colleran et al also reported that EDD responses were significantly greater to both ACh and intravascular flow in collateral arteries of EX rats. Neither blockade of COX with indomethacin nor blockade of endothelial nitric oxide synthase with NG-nitro-L-arginine methyl ester eliminated the increased EDDs. The coronary literature does not consistently indicate enhanced growth of collateral arteries in models of coronary artery disease (CAD) or in patients with CAD after EX. However, it appears that EX has beneficial effects on the vasomotor reactivity of collateral arteries and/or vasomotor control of resistance in collateral-dependent myocardium. For example, it is reported that collateral-dependent coronary arteries exhibited improved EDD and improved adenosine-induced vasodilation in EX animals. EX also improved bradykinin-induced EDD in arterioles from collateral-dependent myocardium and VEGF165-induced EDD was reported to be enhanced in collateral-dependent arterioles. Fogarty et al. (2004) also reported that the enhanced VEGF-induced EDD was mediated principally via increased NO bioavailability. EX appears to increase myogenic tone in arterioles isolated from collateral-dependent zones of models of CAD in a manner similar to that reported for arterioles from normal EX hearts (Laughlin et al. 2012). EX is also reported to enhance endothelin-1-mediated contractile responses in collateral-dependent resistance arteries and to exhibit increased basal tone, and increased K+ channel activity (Laughlin et al. 2010).