Summary: Endothelin-1, a peptide exhibiting extremely potent cerebral vasoactive properties, is elevated in the cerebrospinal fluid after hemorrhagic stroke and impli cated in cerebral vasospasm. The purpose of this study was to determine changes in endothelin in ischemic rat brain by assaying endothelin tissue and extracellular lev els. Immunoreactive endothelin levels in ischemic brain tissue following permanent or transient focal ischemia produced by middle cerebral artery occlusion was deter mined. In addition, endothelin levels were assayed in stri atal extracellular fluid collected by microdialysis before, during, and after global ischemia produced by two-vessel occlusion combined with hypotension. Twenty-four hours after the onset of permanent middle cerebral artery occlusion, the ischemic cortex level (0.58 ± 0.27 fmoll mg protein) of immunoreactive endothelin was signifi cantly (p < 0.05) increased, by 100%, over that in the nonischemic cortex (0.29 ± 0.13 fmollmg protein). TranEndothelin (ET) is a 21-amino acid peptide orig inally isolated from porcine endothelial cells (Yan agisawa et aI., 1988). Three isoforms of endothelin (i.e., ET-l, -2, and -3) have been identified in geno mic DNA (Inoue et aI., 1989). Both ET-l and ET-3 are present in the brain (Matsumoto et aI., 1989; Shinmi et aI., 1989; Takahashi et aI., 1990) and spe cific binding sites have been identified (Koseki et