The authors investigated the effects of nitrous oxide (N20), ganglionic blockade, and combined infusion of epinephrine and norepinephrine (0.1 μg·kg−1·min−1each) on neurologic outcome and brain histopathology in a model of incomplete cerebral ischemia in the rat. Thirty-eight Sprague-Dawley rats were assigned to one of four groups: group 1 (n = 10) received 70% N2O in O2; group 2 (n = 12) received 70% N2O in O2)plus ganglionic blockade; and group 3 (n = 10) received 70% N2O in O2, plus ganglionic blockade and catecholamine infusion. In groups 1–3, ischemia was produced by right carotid occlusion combined with hemorrhagic hypotension (35 mmHg) for 30 min. Group 4 (n = 6) received 70% N2O in O2and hemorrhagic hypotension without carotid occlusion for 30 min. At the end of ischemic and nonischemic hypotension, the carotid artery was unclamped and the blood slowly reinfused. Neurologic outcome was evaluated for a 5-day period with a graded deficit score (0 = normal to 39 = stroke-related death). Brain histopathology was evaluated in coronal section at the level of the caudate nucleus according to a 6-point scale, from 0 = normal to 5 = total hemispheric infarction. Arterial blood gases,pH, and body temperature were kept constant in all groups. Compared to N2O alone (group 1), treatment with ganglionic blockade (group 2) decreased plasma catecholamines by 75% and significantly improved neurologic outcome from incomplete cerebral ischemia (P< 0.05). Administration of exogenous epinephrine and norepinephrine in the presence of N2O and ganglionic blockade (group 3) worsened neurologic outcome compared to group 2 (P< 0.05). Brain histopathology in rats surviving the 5-day examination period showed an entire range of brain tissue damage in the ischemic hemisphere. However, neurologic deficit did not predict histopathologic neuronal injury. No neurologic deficit or histopathologic damage was seen in rats treated with nonischemic hemorrhagic hypotension (group 4). The improvement of neurologic outcome after ganglionic blockade suggests direct involvement of the sympathetic nervous system in the modulation of ischemic brain damage.