Accumulation of L-alpha-aminoadipate by rat cerebral cortical slices is a stereospecific and Na+-dependent process. The uptake of this compound is also temperature-dependent, with a Km of 1.6 X 10(-4)M for the high-affinity system. D-alpha-Aminoadipate has characteristics similar to those displayed by the L-isomer but to a lesser degree. L-Glutamate and L-aspartate inhibit the uptake of L-alpha-aminoadipate. D- and L-alpha-Aminoadipate are, respectively, weak uncompetitive and weak competitive inhibitors for the uptake of L-glutamate and L-aspartate. Both enantiomers inhibit GABA uptake but in quite different ways. The release of L-alpha-aminoadipate from the cerebral cortical slices is stimulated by a high concentration of K+ ions in the presence of Ca2+ in the perfusion buffer; the D-isomer displays this property to a lesser degree. The omission of Ca2+ markedly reduces the release of these two compounds. Less than 10% of the preloaded D- and L-alpha-aminoadipate are metabolized by the cerebral cortex during 40 min of superfusion. The possibility of L-alpha-aminoadipate as a neurotransmitter candidate is discussed.