1. With the use of whole cell recordings of layer V cells from slices of rat visual cortex, we demonstrate a potentiation of the response to N-methyl-D-aspartate (NMDA) by the metabotropic glutamate agonist (1S,3R)-1-Amino-1,3-cyclopentanedicarboxylic acid. This potentiation occurs within a few seconds and lasts a few minutes. 2. The potentiation is seen with tetrodotoxin in the perfusion solution, but is abolished by guanosine 5'-0- (2-thiodiphosphate) in the pipette solution, showing that it is a postsynaptic phenomenon. The potentiation is also abolished by alpha-methyl-4-carboxyphenylglycine in the bath solution, confirming that it is due to metabotropic glutamate receptors. 3. In 29 of 31 cases tested, the response to alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid was also potentiated, and the potentiation remained in the presence of the NMDA antagonist D-2-amino-5-phosphonovalerate.