Endothelin-mediated vasoconstriction may theoretically aggravate ischemic neuronal damage. Although investigators have demonstrated that endothelins are produced by cerebral microvessel endothelial cells, astrocytes and neurons in vitro, whether endothelins are produced during cerebral ischemia is still unclear. The purpose of this study, therefore, was to measure endothelin-1 in brain tissue and plasma following middle cerebral artery occlusion and to examine the relationship between brain tissue and plasma endothelin-1 levels. The middle cerebral artery of rabbits was occluded for 2, 4 or 24 h. The amount of endothelin-1 in both brain tissue and plasma was determined by RIA. The results demonstrate that the concentrations of endothelin-1 in the ischemic brain tissue and plasma are both significantly increased after focal cerebral ischemia (P < 0.01). The data confirm that an acute and marked increase of endothelin-1 in brain tissue and plasma is associated with focal ischemic events. The possibility that endothelin-1 has a role in neuronal cell damage following focal ischemia warrants further attention.