We have previously shown that beta-amyloid (Abeta) increased the excitotoxicity of ibotenate, an N-methyl-D-aspartate (NMDA) receptor agonist, to hippocampal neurons of rats. In this report, non-toxic amounts of kainate were co-injected with Abeta into rat hippocampus. Nissl-stained brain sections revealed that Abeta/kainate co-injection exerted synergistic neuronal degeneration in the hippocampus as well as that by Abeta/ibotenate co-injection. MK-801, an NMDA receptor antagonist, blocked the neuronal loss induced by Abeta/ibotenate co-injection, but not by Abeta/kainate co-injection. On the other hand, 6-cyano-7-nitroquinoxaline-2, 3-dione, a kainate receptor antagonist, suppressed the neuronal loss induced by the Abeta/kainate co-injection, but not that by the Abeta/ibotenate co-injection. This suggests that Abeta increases the sensitivity of both the NMDA receptor and the kainate receptor.