Ibotenate, a rigid structural analogue of glutamate, markedly enhances the hydrolysis of membrane inositol phospholipids, as reflected by the stimulation of [³H]inositol monophosphate formation in rat hippocampal slices prelabeled with [³H]inositol and treated with Li⁺. Quisqualate, homocysteate, l‐glutamate, and l‐aspartate also induce a significant (albeit weaker) increase in [³H]inositol monophosphate formation, whereas N‐methyl‐d‐aspartate, kainate, quinolinate, and N‐acetylaspartylglutamate are inactive. The increase in [³H]inositol monophosphate formation elicited by the above‐mentioned excitatory amino acids is potently and selectively antagonized by dl‐2‐amino‐4‐phosphonobutyric acid, a dicarboxylic amino acid receptor antagonist. These results suggest that, in the hippocampus, a class of dicarboxylic amino acid recognition sites is coupled with phospholipase C, the enzyme that catalyzes the hydrolysis of membrane inositol phospholipids.