Previous studies have shown that potassium-evoked, calcium-dependent, endogenous aspartate release is greater from hippocampal slices of adult epileptic (EL) mice than from nonepileptic control C57BL/6J (B6) mice. To examine further the association between epilepsy and enhanced aspartate release in EL mice, endogenous neurotransmitter release from hippocampal slices was studied in young, seizure-free EL mice and in two nonseizure control mouse strains, DDY and B6. DDY is the parental strain from which EL arose, and it has a genetic background similar to EL. Released amino acid neurotransmitters were quantitated by HPLC with fluorescent detection and were expressed as picomoles of amino acid released per minute of incubation per slice +/- SEM. Aspartate release was significantly higher in EL mice (15.8 +/- 0.8) than in either the control B6 or DDY mice (8.5 +/- 1.4 and 8.4 +/- 1.7, respectively). No significant differences were found among the B6, DDY, and EL mice for the release of glutamate (23.0 +/- 2.0, 32.3 +/- 5.8, and 25.9 +/- 2.6, respectively) or GABA (23.5 +/- 0.7, 19.5 +/- 3.2, and 21.8 +/- 3.2, respectively). Thus, enhanced aspartate release precedes the onset of EL seizures and may be related to the cause rather than to the effects of seizure activity.