Using brain microdialysis we studied the effect of high doses of monosodium glutamate (MSG) on the extracellular concentration of glutamate in the hypothalamus and in the hippocampus of freely moving rats. MSG at 4 g/kg (40% solution) given by gavage caused a significant increase in plasma (5.3 +/- 0.4-fold, P <0.01) and extracellular glutamate in the hippocampus (4.2 +/- 0.6-fold, P <0.01) and in the hypothalamus (8.9 +/- 1.7-fold, P <0.01) compared to control rats receiving a 40% sucrose solution (10 ml/kg). The peak increase was found within 40 min after MSG administration then declining to baseline in the next 80 min. No changes were found in glutamate tissue concentrations. Twenty-one days after ad libitum MSG intake with the diet (approximately 4 g/kg) no changes were found, in plasma, in extracellular and tissue concentration of glutamate in the hypothalamus compared to rats fed with a normal diet. Glutamate release induced by 200 mM KCl was not modified as well. Histological analysis of Nissl-stained brain tissue slices did not reveal any obvious cell loss in the hippocampus and hypothalamus after acute or chronic MSG administration.