The metabolism of glutamate, taken as an index of the metabolic state of the brain, was studied in brains of 3-, 12- and 30-month-old rats. Following the injection of a mixture of [3H]acetate and d-[2-14C]glucose, the brain levels of glutamate and aspartate were decreased in 30-month-old rats when compared with those of 3-month-old rats. No significant age-related differences were found in glutamine levels. Neither the protein levels nor the incorporation of the radioactivity in brain proteins differed among the three age groups, suggesting that there are no age-related differences in protein synthesis. The incorporation of d-[2-14C]glucose in aspartate and glutamine, expressed as the respective relative specific activities (RSA: specific activity of amino acid/specific activity of glutamate), did not change with age. Since glucose is the precursor of the large glutamate pool in brain, it can be concluded that no age-related changes occur in the metabolism of glutamate in the large compartment. The incorporation of [3H]acetate into aspartate, expressed as the RSA, did not differ among the age groups. The RSA of 3H-labelled glutamine, however, was significantly decreased 10 minutes after injection of the precursor mixture in brains of 30-month-old rats when compared with those of 3-month-old rats. This difference had disappeared 20 minutes after injection, suggesting a somewhat delayed metabolism of glutamate in the small compartment, for which acetate is a precursor. These results and all the other parameters measured indicate that no large age-related metabolic changes in rat brain occur. Chemicals/CAS: glutamic acid, 11070-68-1, 138-15-8, 56-86-0, 6899-05-4; Acetates; Aspartic Acid, 56-84-8; Glucose, 50-99-7; Glutamates; Glutamine, 56-85-9