Glutamine synthetase (GS) activity was measured in whole brain, different brain areas, liver and heart of 23- to 26-month-old rats, and then compared to matched animals of 3 months. A significant increase of GS activity was found in whole brain (25%) of old rats, as well as in all brain areas studied, but particularly in midbrain (36%), hypothalamus (32%), brainstem (32%), striatum (27%) and cerebellum (22%). A significant decrease of GS activity (21%) was found in liver and no significant difference in heart of old rats when compared to matched animals of 3 months. The present results suggest that an increase of GS activity in brain of old rats may be an adaptive phenomenon, and the regulatory mechanisms for GS with increasing age are different, depending on the tissues.