Felbamate is an antiepileptic drug whose action appears to occur mainly through an interaction with neurotransmission mediated by excitatory amino acids. We assessed its effectiveness in a model of transient global ischaemia in Mongolian gerbils. Dizocilpine (MK 801) was used for comparison. Treatment was given 10 min after transient forebrain ischaemia which was performed by occluding both common carotid arteries for 10 min. Felbamate (300 mg/kg i.p.) increased the number of surviving neurons in the CA1, CA2 and CA3 hippocampal cells. In particular, the CA1 area had a significantly higher number of surviving pyramidal neurons than that of vehicle-treated animals (67 +/- 11 vs 33 +/- 6 surviving neurons/mm; P < 0.05). No significant difference in density of surviving neurons was observed between dizocilpine (3 mg/kg i.p.) and vehicle (54 +/- 10 vs 33 +/- 6 surviving neurons/mm). The EEG results indicated that the effect of felbamate, used alone, is the same in the ischaemic-vehicle group as non-ischaemic group. Our results show that felbamate exerts neuroprotective effects in a model of severe cerebral ischaemia.