Using a special tetrazolium salt technique, a striking correlation was observed between Na+ concentration of the incubation medium and the formation of formazan catalyzed by glutamate dehydrogenase (GDH) in glutamatergic neuropil areas of the hippocampal formation, cerebellum, and other brain regions. Na+ concentrations of 130-150 mmol/l caused maximal formazan production. The GDH catalyzed sodium-dependent increase in formazan production is suggested to be a consequence of the sodium dependence of glutamate uptake in glutamatergic brain structures supplying the enzyme with substrate.