Age-dependent changes in the expression of group III metabotropic glutamate receptors (mGluR4 and mGluR7) were studied by quantitative in situ hybridization using male Fisher 344 rats 3, 12 and 25 months of age. Results indicate an early decrease in mGluR7 mRNA level in several cortical areas including the frontal, parietal and temporal cortices. In the hippocampus, mGluR7 mRNA levels decreased in the CA1 region and the lower blade of the dentate gyrus. Moreover, significant decrease was found in the laterodorsal thalamic nucleus at 12 months of age. Other regions such as the caudate putamen and nucleus accumbens showed no age-related changes in mGluR7 mRNA levels. Analysis of emulsion autoradiograms revealed a 36% decrease of mGluR7 mRNA in Purkinje neurons in the 12-month-old group and a 48% decline in the 25-month-old group as compared to the 3-month-old group. A substantial decrease in mGluR4 mRNA level was found in the granule cell layer of the cerebellum during aging. The difference between the young and aged groups exceeded 35%. These region-specific decreases may have important implication in some of the age-related changes in cognitive, motor and/or sensory functions.