The effect of the glutamate analogue L-alpha-aminoadipate (alpha AA) on the release of glutamate and gamma-aminobutyric acid (GABA) from rat hippocampal slices was investigated in vitro. Oxygen/glucose deprivation caused a large release of glutamate and GABA. alpha AA added during energy deprivation reduced the glutamate release in a dose-dependent manner (56% reduction at 5 mM), whereas GABA release was unchanged. We speculate that ischemic glutamate release from the brain is mediated by a low affinity transport mechanism that is blocked by alpha AA.