There is growing evidence for several different roles for purines in the control of blood flow. (1) Adenosine 5′-triphosphate (ATP) acts as a cotransmitter with noradrenaline and neuropeptide Y released from sympathetic perivascular nerves. In most vessels it acts via P2x-purinoceptors to produce vasoconstriction synergistically with α-adrenoceptor activation, while in some coronary vessels it appears to act via P2y-purinoceptors to produce vasodilatation in concert with β-adrenoceptor activation. (2) Adenosine, via P1-purinoceptors, acts as a prejunctional modulator of transmitter release from perivascular nerves; it also acts directly on vascular smooth muscle to produce vasodilatation. (3) ATP is stored in and released from vascular endothelial cells (including those from the coronary bed) during changes in blood flow or during hypoxia, and acts via P2Y-purinoceptors on endothelial cells to release endothelium-derived relaxing factor, resulting in vasodilatation. (4) ATP may be released together with substance P and calcitonin gene-related peptide from some sensory nerves during ‘axon-reflex’ activity when antidromic impulses pass down collaterals supplying blood vessels. (5) Finally, there is evidence to suggest that ATP released from intrinsic (non-sympathetic) neurones in the airways and heart has potent actions on the resistance vessels.