The expression of long-term potentiation (LTP) in area CA1 of hippocampus has been proposed to result from an increased sensitivity of the AMPA/quisqualate receptors. We have investigated the binding properties of excitatory amino acid receptors in phospholipase A2 (PLA2)-treated rat brain membranes. PLA2 from bee venom produced a significant increase in the binding of [3H]-AMPA ([3H]-amino-3-hydroxy-5-methylisoxazole-4- propionate), a ligand for the AMPA/quisqualate receptor. Analysis of the saturation kinetics revealed that PLA2 treatment increased the affinity of the AMPA/quisqualate receptor without changing the maximum number of sites. In contrast, PLA2 treatment did not detectably modify the binding of [3H]-kainate to the kainate receptor and of [3H]-glutamate and [3H]-glycine to the NMDA (N-methyl-D-aspartate) receptor complex. These finding suggest that phospholipase A2 may regulate the AMPA/quisqualate receptor and could play an important role in the development of LTP.