AMPA antagonists have been shown to be remarkably neuroprotective in models of global ischemia, but the data in focal ischemia remain controversial. We, therefore, studied the dose-response characteristics and the time window of efficacy of the AMPA antagonist NBQX in a rat model of permanent focal ischemia. NBQX 40, 60 or 100 mg/kg i.v., substantially reduced infarct size. Neuroprotection was maintained when the initiation of drug administration was withheld for 15, 45 or 90 min after permanent middle cerebral artery occlusion. Furthermore, NBQX did not induce heat shock protein in cingulate cortex, as do some N-methyl-D-aspartate antagonists. Thus, the compound is a potent neuroprotectant in focal ischemia and has an unusually long time window of effectiveness.