We demonstrate that the enzyme family responsible for the restoration of the transmembrane cation balance, namely the sodium pump (Na+, K(+)-ATPase), plays a critical role in whether glutamate injures adult neurons in vivo. Partial inhibition of the sodium pump by the cardiac glycoside ouabain in young adult rats is not itself damaging. This treatment, however, markedly potentiates ordinarily subtoxic dosages of the glutamate analog kainic acid to produce limbic seizures and widespread neurodegeneration within the hippocampus in a pattern closely resembling that observed for human temporal lobe epilepsy.