Dual control of local blood flow by purines is described: (1) adenosine 5’-triphosphate (ATP) released as a cotransmitter with noradrenaline from perivascular sympathetic nerves acts on P2X-purinoceptors on smooth muscle cells to produce vasoconstriction; (2) ATP released from endothelial cells during hypoxia (and ADP released from aggregating platelets) acts on P2Y-purinoceptors on endothelial cells which results in production of endothelium-derived relaxing factor and subsequent vasodilatation. It is suggested that the endothelial-mediated vasodilatation is a pathophysiological mechanism to protect the host tissue (e.g. brain or heart) from damage produced by hypoxia following ischaemia. The ATP released from the endothelial cells is rapidly broken down to adenosine which augments this protective mechanism by acting directly on P1-purinoceptors on vascular smooth muscle to produce a longer lasting component of vasodilatation and on perivascular sympathetic nerve terminals to inhibit release of excitatory neurotransmitters. The possibility that impairment of normal endothelial-mediated responses in atherosclerosis and hypertension can lead to local vasospasm is considere