Metabotropic glutamate receptors (mGluRs) have been implicated in a number of hippocampal functions including learning and memory. Five subtypes have been molecularly and pharmacologically characterized. Using in situ hybridization with oligonucleotide probes selective for these five mGluRs, we have found that each has a unique pattern of expression in the hippocampus and entorhinal cortex. mGluR1 is expressed predominantly in the dentate gyrus and CA3. mGluR2 is enriched in the dentate gyrus and inner layer of the entorhinal cortex. mGluR3 is also expressed in these two structures, but unlike all the other mGluRs, is found in white matter areas as well. mGluR4 is present predominantly in CA2 while mGluR5 is concentrated in most regions of the hippocampus and entorhinal cortex. Comparative analysis of the distributions of these receptors with that of the components of their putative downstream signal transduction mechanisms suggests that mGluR5 may be the main subtype of mGluR which mediates the excitatory actions of glutamate in CA1 and could contribute to the elevation of calcium levels found in CA1 pyramidal neurons in long term potentiation and in ischemic/hypoxic injury. mGluR2 and mGluR3, the main subtypes contributing to the inhibitory actions of glutamate, are absent in CA1. Thus, the mGluR-mediated excitatory actions of glutamate can occur in all regions of the hippocampus whereas the mGluR-mediated inhibitory actions of glutamate may be restricted to the dentate gyrus and CA3.