Using a special tetrazolium salt technique, a striking correlation was observed between Na+ concentration of the incubation medium and the activity of glutamate dehydrogenase (GDH) in glutamatergic neuropil areas of the hippocampal formation, cerebellum, and other brain regions. Na+ concentration of 130 to 150 mmol/l caused maximal formazan production. The histochemical enzyme reaction in neuronal perikarya as well as biochemically estimated GDH activity were found to be rather inhibited by such Na+ concentrations. The GDH catalyzed sodium dependent increase in formazan production is discussed to be a consequence of the sodium dependence of glutamate uptake in glutamatergic brain structures supplying the enzyme with substrate.