Glutamate is thought to be the excitatory neurotransmitter in the lateral geniculate nucleus (LGN) of the cat, mediating visual transmission from the retina via ionotropic receptors of both D,L-alpha-amino-3-hydroxy-5-alpha-methyl-4-isoxazolepropionate and N-methyl-D-aspartate subtypes. Moreover, glutamate also exerts an important modulatory influence on LGN cells, where metabotropic glutamate receptors (mGluRs) seem to play a crucial role. Here we show in anesthetized adult cats that iontophoretic application of the specific mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) produced two, distinctly different, effects on LGN neurons. Visual responses to flashing spots and drifting gratings were attenuated (decreased by an average of 59%) in 13 of 23 of the cells but augmented (increased by an average of 60%) in 10 of 23 of the cells. Further, in each case when the specific mGluR5 agonist (R,S)-2-chloro-5-hydroxyphenylglycine was applied, the effects obtained were the opposite to those of MPEP. Data obtained in a second group of experiments to determine a possible interaction between mGluR5 blockade by MPEP and glutamate ionotropic receptors show that, in the majority of neurons (11 of 15, 73%), the MPEP-mediated effects seem to be independent of N-methyl-D-aspartate and D,L-alpha-amino-3-hydroxy-5-alpha-methyl-4-isoxazolepropionate receptor activity. Our results demonstrate a physiological role for mGluR5 in controlling retinal input and show, in vivo, a more intricate scenario than previously suggested, highlighting the complexity of metabotropic receptor interactions with excitatory and inhibitory elements in the thalamus.