Mild hypothermia has been recently proposed as a therapeutic approach for ameliorating ischaemic cerebral damage. The protective potential of mild hypothermia, however, may be dependent on its ability to reduce the efflux of potentially excitotoxic amino acids and the severity of ischaemia. In this study, we examined the effects of mild brain hypothermia (33 degrees C) in a rabbit model of permanent focal ischaemia. In vivo microdialysis was used to measure extracellular amino acids in central and peripheral regions of the ischaemic cortex. In normothermic ischaemia (n = 7), glutamate, alanine, taurine, and phosphoethanolamine increased above baseline levels by about 2 h post-ischaemia. Mild hypothermia (n = 7) reduced glutamate efflux only in the central regions and increased alanine efflux in the peripheral regions of ischaemia. There were no significant differences in other amino acid levels between the two temperature groups. Haematoxylin-eosin histology did not demonstrate hypothermic protection in the ischaemic hemisphere. The lack of neuroprotection in this study may correspond with the sustained release of glutamate in the peripheral regions of ischaemia even with lowered brain temperature. These results suggest that hypothermic reduction of excitotoxic perturbations may be more important in the ischaemic periphery than the core.