Decreased plasma and muscle glutamate concentrations have been observed in patients with chronic obstructive pulmonary disease (COPD), suggesting disturbances in glutamate metabolism. The present study was conducted to further examine glutamate metabolism in 8 male COPD patients (68 +/- 4 y) by measurement of whole-body (WB) glutamate production and splanchnic glutamate extraction in the postabsorptive state as well as in response to feeding. Because COPD is particularly prevalent in the elderly and aging per se may also affect glutamate metabolism, 2 male control groups were included: 8 healthy elderly (63 +/- 3 y) and 8 young (22 +/- 1 y) subjects. On 2 test days, the stable isotope L-15N-glutamate was infused i.v. or enterally according to a primed constant and continuous infusion protocol. After 90 min of infusion, subjects ingested a carbohydrate-protein drink (28% milk protein, 72% maltodextrin) every 20 min for 2 h. Arterialized-venous blood samples were taken at the end of the postabsorptive and feeding periods. Postabsorptive WB glutamate production and splanchnic glutamate extraction were significantly lower in the elderly and COPD patients than in the young (P < 0.01). Feeding further decreased WB endogenous glutamate production in the elderly and COPD patients, with COPD patients tending (P = 0.07) to have a greater decrease. Splanchnic glutamate extraction increased during feeding in the elderly (P < 0.05) but did not change in COPD patients. In conclusion, aging reduces postabsorptive WB endogenous glutamate production and splanchnic glutamate extraction. COPD does not affect postabsorptive WB glutamate metabolism but may influence splanchnic glutamate metabolism during feeding.