Abstract The involvement of endothelins in the cerebrovascular events which follow a focal ischemic insult in the rat was explored in the present study. Intravenous (i.v.) administration of bosentan (3, 15 and 30 mg/kg), an endothelin ET A and ET B receptor antagonist, prior to middle cerebral artery occlusion in the rat did not significantly alter cortical perfusion in these rats. A 62 ± 3% reduction in laser doppler flow was observed 10 min after middle cerebral artery occlusion in the vehicle-treated group compared to a 49 ± 5% reduction in laser doppler flow in the group receiving 15 mg/kg bosentan. Pre-treatment with intravenous bosentan (15 mg/kg) prior to middle cerebral artery occlusion in the rat also failed to elicit significant alterations in the reduction in regional cerebral blood flow (frontal cortex; 81 ± 13 ml/100 g/min) and subsequent hemispheric volume of ischemic damage observed (94 ± 9 mm 3) compared to the vehicle treated animals (68 ± 9 ml/100 g/min, 113 ± 5 mm 3, respectively). Minimal changes were also observed in these endpoints, when a 15 mg/kg dose of bosentan was administered following middle cerebral artery occlusion. In conclusion bosentan failed to expose a major role for endothelins in focal ischemic pathology in the rat.