By selective chemical stimulation of the subthalamic nucleus (STh) with the gamma-aminobutyric acid (GABA) antagonist bicuculline, we have studied the effect of its projections to the target nuclei. Results show that bicuculline (0.39 mM) produced a mean activation of 358% in subthalamic neurons. Most of the cells recorded in the substantia nigra pars reticulata (SNpr), the entopenduncular nucleus (EP), and the globus pallidus (GP) were also significantly activated. In the substantia nigra pars compacta (SNpc), slight and opposite changes were produced: half of the cells were activated and half were inhibited. In the striatum, 3 types of responses were recorded: activation, inhibition, and biphasic effect. Inhibition of subthalamic neurons by local microinjection of muscimol (0.95 mM), produced reductions in the neuronal activity of cells in the SNpr, the EP, and the GP. These results suggest that the STh conveys an important and permanent excitatory influence onto its target nuclei. In another set of experiments, in order to investigate whether or not the STh utilizes glutamate for neurotransmission in the SNpr, we injected the glutamate receptor antagonist kynurenic acid (2.6 mM) into the SNpr, later followed by an injection of bicuculline in the STh. Kynurenic acid alone produced a mean inhibition of 30% in non-dopaminergic nigral cells, and antagonized the subsequent bicuculline-induced activating effect of the STh. These results further confirm recent data showing that the STh exerts an excitatory action on its efferent structures, and provide new evidence for glutamatergic transmission in subthalamic projections.(ABSTRACT TRUNCATED AT 250 WORDS)