Administration of the non-competitive NMDA receptor antagonist MK-801 (5-methyl-10,11-dihydro-5H-dibenzo[1,d]cyclohepten-5,10- imine) produces paradoxical neurotoxicity in limbic cortical regions which include the entorhinal cortex. The expression of NMDAR-2C but not -2A, -2B or -2D subunits was significantly decreased in rat entorhinal cortex layer III following MK-801 administration. These results suggest an important role for the NMDAR-2C subunit in the response to MK-801-induced neurotoxicity in brain regions highly vulnerable to injury.