The metabotropic glutamate receptor, mGluR1 alpha, is postsynaptic in excitatory synapses in many populations of neurons and mediates long-term responses. The present study defines the distribution of this receptor using a new, highly specific monoclonal antibody to mGluR1 alpha. Overall distribution of immunostaining was similar to that described previously with polyclonal antibodies, including prominent staining in the olfactory bulb, interneurons of the CA1 hippocampus stratum oriens/alveus, globus pallidus, thalamus, Purkinje cells and in cells of the outer dorsal cochlear nucleus and with little or low staining in principal cells of the cerebral cortex and hippocampus. Interestingly, the well-known association of mGluR1 alpha receptors with neocortical interneurons was even more prevalent than previously noted with polyclonal antibodies. Ultrastructural studies in the hippocampus and cerebellum showed dense immunoperoxidase staining in postsynaptic membranes and densities and in perisynaptic and extrasynaptic membranes, as well as substantial cytoplasmic staining associated with organelles, especially the endoplasmic reticulum.