Abstract In rats, the seizures induced by systemic kainic acid (KA) are followed by extensive neuronal damage, notably in the hippocampal region. We report that the specific N- methyl- d-aspartate (NMDA) receptor antagonist, d-(−)-aminophosphonovalerate (D(−)APV), given i.c.v. prior to or 2 h after i.p. KA injection markedly protected CA1 but not other hippocampal neurons against degeneration. In contrast, D(−)APV had no effect on KA-induced wet dog shakes or on behavioral seizures. We conclude that NMDA receptors participate in the neurotoxic but not in the behavioral effects of systemic KA.