Glutamate, a major neurotransmitter in the brain, is also involved in pathophysiological processes resulting in secondary lesions following ischaemia or trauma. In the present study we investigated the relationship between glutamate excitotoxicity free radical induction (indicated by ascorbic acid level) and glucose-lactate metabolism. Monosodium glutamate was applied through microdialysis probes (500 mM in perfusate) into the cortex of rats for 30 minutes and ascorbic acid (ASC), glucose (GLUC) and lactate (LAC) were measured in dialysates. Glutamate produced a cortical lesion with an average volume of 12.7 +/- 1.4 mm3. Analysis of dialysates revealed a significant increase of ASC (325 +/- 52% of baseline) and LAC (677 +/- 86%) in the core lesion. In the lesion periphery a non-significant and short-lasting elevation was measured for both parameters with a second microdialysis probe (about 1.3 mm frontally to the first probe). A concomitant decrease of GLUC was found in both probes, reaching 29 +/- 8% and 60 +/- 7% of basal levels in the core and periphery of the lesion, respectively. In addition, we studied the delivery characteristics of several glutamate concentrations (10, 100 or 1000 mM in perfusate) during a 90-minute application into the cortex. The delivery of glutamate from the perfusate to the brain was about 33-38% in the first 30 min and afterwards 11 25% of the total in the perfusate. The results show that cortical application of glutamate changes the composition of the extracellular fluid, which could contribute to the development of the lesion.