TWO NEWLY-DEVELOPED COMPOUNDS (U92798 and U92032), which inhibit lipid peroxidation and block calcium entry, were studied for their effects on neocortical damage after transient focal ischemia. Ischemia was induced in Sprague-Dawley rats by simultaneous occlusion of the left middle cerebral artery and both common carotid arteries for a period of 3 hours. Compounds (1 mg/kg) were administered intravenously 30 minutes before occlusion and again 2.5 hours after the cessation of blood flow. After a 72-hour period of reperfusion, the animals were killed and examined for cerebral infarction and edema. Treatment with U92798 or U92032 significantly reduced the volume of cortical infarction. Edema was also reduced in these groups; however, this effect did not achieve statistical significance. These results suggest that dual function compounds, which both inhibit lipid peroxidation and block calcium entry, are promising therapeutic agents for the amelioration of ischemic cerebral damage.