The aim of this study was to investigate the effects of preconditioning on amino acid neurotransmitter release, induced by hypoxia/hypoglycaemia, from rat brain cortical slices. Tissue, perfused with artificial cerebrospinal fluid (aCSF) at 37 degrees C with zero glucose and gassed with 95% nitrogen and 5% carbon dioxide, showed a fivefold increase in glutamate release with little effect on gamma-aminobutyric acid (GABA) release. Preconditioning, with three 5-min periods of hypoxia/hypoglycaemia preceding continuous hypoxia/hypoglycaemia, significantly decreased glutamate release whilst significantly elevating GABA release. These results suggest that GABA may reduce the release of glutamate and consequently decrease the neurotoxic effects of glutamate.