In vivo microdialysis in freely moving rats was used to investigate the influence of the indirect dopamine receptor agonist levodopa (L-DOPA), alone and combined with the N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine (MK801), on extracellular glutamate levels in the striatum of intact and 6-hydroxydopamine-lesioned rats. L-DOPA (25 mg/kg i.p. after benserazide 10 mg/kg i.p.) increased extracellular glutamate levels in the striatum of both intact and dopamine-depleted rats. A prior injection of MK801 (0.1 and 1.0 mg/kg i.p.) did not alter the L-DOPA-induced glutamate release in the striatum of intact rats. In contrast, the L-DOPA-induced increase in glutamate in the striatum of 6-hydroxydopamine-lesioned rats was suppressed by MK801 (0.1 mg/kg i.p.). The data presented here suggest that NMDA receptors do not play a role in the L-DOPA-induced increase in striatal glutamate in intact rats but are involved in the glutamate release in the dopamine-depleted striatum. The suppression of this increase by prior administration of MK801 could represent a neuroprotective effect.