Effects of excitatory amino acid receptor antagonists and voltage-dependent Ca(2+) channel antagonists on ischemia-induced intracellular free Ca(2+) accumulation in rat hippocampal slices were examined. Ischemia caused a large Ca(2+) accumulation in CA1 region but a small Ca(2+) accumulation in CA3 and dentate gyrus regions. When applied during ischemia, the NMDA receptor antagonist MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine maleate) inhibited the ischemic Ca(2+) accumulation only in the CA1, but the non-NMDA receptor antagonist CNQX (6-cyano-7-nitroquinoxaline-2,3-dione) inhibited it in all the three regions. The L-type Ca(2+) channel antagonists nifedipine and verapamil inhibited the ischemic Ca(2+) accumulation only in the CA1 region, but omega-conotoxin, a N- and L-type Ca(2+) channel antagonist inhibited the Ca(2+) accumulation in all the three regions of the hippocampus. When applied after 5-min ischemia, nifedipine but not MK-801, inhibited sustained postiscehmic Ca(2+) elevation in the CA1 region but not in the CA3 and dentate gyrus regions. These findings suggest that the enhanced ischemia-induced Ca(2+) accumulation in the CA1 region is mediated via activation of both NMDA receptors and L-type-like Ca(2+) channels. It appears that sustained postischemic Ca(2+) elevation in the CA1 region is mediated via activation of L-type-like Ca(2+) channels, but not of NMDA receptors.