Clonidine decreases central sympathetic activity and anesthetic requirement. We tested whether clonidine improves outcome from incomplete ischemia of the brain in rats. Control rats were anesthetized with 25 micrograms.kg-1.h-1 of intravenous fentanyl and inhalation of 70% nitrous oxide (N2O). Clonidine-treated rats received fentanyl/N2O and 10 micrograms/kg of intravenous clonidine 10 min before ischemia, which was produced by right carotid ligation combined with hemorrhagic hypotension to 35 mm Hg for 30 min. Clonidine increased plasma glucose before ischemia and decreased blood catecholamine concentrations during ischemia compared with the control group. Neurologic outcome was evaluated daily for 3 days after ischemia and histopathology was performed at the end of this period. Clonidine significantly improved neurologic outcome on each of the 3 days after ischemia. Histopathology was severe in the control group but not enough rats survived in this group for statistical analysis. The authors conclude that clonidine decreases sympathetic activity during ischemia and that this is associated with an improvement in outcome from incomplete ischemia.