BLOCKADE of adenosine receptors can reduce cerebral infarct size in the model of global ischaemia. Using the potent and selective A2Aadenosine receptor antagonist, SCH 58261, we assessed whether A2Areceptors are involved in the neuronal damage following focal cerebral ischaemia as induced by occluding the left middle cerebral artery. SCH 58261 (0.01 mg/kg either i.p. or i.v.) administered to normotensive rats 10min after ischaemia markedly reduced cortical infarct volume as measured 24 h later (30%vscontrols,p< 0.05). Similar effects were observed when SCH 58261 (0.01 mg/kg, i.p.) was administered to hypertensive rats (28% infarct volume reductionvscontrols,p< 0.05). Neuroprotective properties of SCH 58261 administered after ischaemia indicate that blockade of A2Aadenosine receptors is a potentially useful biological target for the reduction of brain injury.