Many discrepancies still exist regarding the effects of dopamine on the activity of subthalamic neurons (STN). The aim of the present study was to investigate whether dopamine and its receptor agonists indeed modulate amino acid release, monitored by means of in vivo microdialysis, in the STN of intact and 6-hydroxydopamine (6-OHDA) lesioned rats. In intact rats, subthalamic dopamine perfusion via the microdialysis probe induced a significant increase in subthalamic extracellular (EC) glutamate levels. EC GABA levels showed a tendency towards a increase. Perfusion of the dopamine D₁ agonist SKF38393 induced a significant increase in subthalamic EC glutamate levels and a significant decrease in EC GABA levels. The D₂ agonist quinpirole only induced a significant increase in EC GABA levels. In 6-OHDA lesioned rats, the dopamine-induced increase in EC glutamate levels, as observed in intact rats, was completely abolished, but the GABA levels decreased significantly. The D₁- receptor mediated increase in EC glutamate levels as seen in intact rats was also abolished in the 6-OHDA lesioned rats. However, the decrease in EC GABA was sustained. Finally, the quinpirole-induced increase in EC GABA observed in intact rats was abolished in the 6-OHDA lesioned rats. These results point out a clear, but complex dopaminergic modulation of neurotransmitter release in the subthalamic nucleus of the rat. Furthermore, it seems that this modulation is altered in 6-OHDA lesioned rats.