L-Glutamate, N-methyl-D-aspartate, quisqualate and potassium chloride enhanced Ca2+ accumulation by rat cortical slices as determined using 45Ca2+ uptake and Ca2+ mobilisation in cortical synaptosomes as determined using quin-2 fluorescence. Quinolinate and kainate were ineffective. Responses to L-glutamate and N-methyl-D-aspartate were blocked by non-competitive (ketamine, phencyclidine, Mg2+) and competitive (2-amino-5-phosphonovalerate) antagonists. These data suggest that activation of excitatory amino acid receptors in the cortex results in enhanced Ca2+ mobilisation which can be blocked by selective antagonists. Such effects may be related to neurotoxic properties of the excitatory amino acids and the neuroprotection afforded by excitatory amino acid antagonists.