The technique of intracerebral microdialysis was employed to assess the effect of acute clozapine and haloperidol on the extracellular levels of aspartate and glutamate in the striatum and medial prefrontal cortex of conscious rats. Subcutaneous injection of 25 mg/kg clozapine, but not the lower dose of 15 mg/kg, led to a significant increase in both aspartate and glutamate levels over time. The maximum effect was observed two hours after injection. Haloperidol (0.5 and 1 mg/kg s.c.) did not increase the extracellular levels of aspartate and glutamate over time. At all doses tested, both drugs were without a significant effect in the striatum. These data suggest that clozapine may have selective actions on the cortical excitatory amino acid systems.