The activity of subthalamic neurons was recorded extracellularly in anaesthetized rats after stimulation, inhibition or lesioning of the parafascicular nucleus. Electrical stimulation of the parafascicular nucleus evoked a complex response with two excitatory phases. The first response was correlated with a monosynaptically-driven excitation via a parafascicular input to the subthalamic nucleus. Since the second phase was observed even when the early excitation was not recorded and was eliminated by lesion of the globus pallidus, we suggest that it is not generated by a mechanism intrinsic to the subthalamic nucleus and is due to a disinhibitory effect originating from the globus pallidus. Microinjection of carbachol into the parafascicular nucleus enhanced by 119% the discharge rate of the neurons in the ipsilateral subthalamic nucleus and that of muscimol decreased the discharge rate by 91%. Opposite changes, a decrease of the discharge rate of 49% after microinjection of carbachol and an increase of 47% after muscimol, occurred in the contralateral subthalamic nucleus. In contrast to the above results, the unilateral excitotoxic lesion of the parafascicular nucleus, performed one week before recording, decreased the discharge rate by 69% of the ipsilateral subthalamic nucleus neurons and by 34% that of the contralateral neurons. We suggest that the parafascicular input to the subthalamic nucleus is an excitatory pathway which can tonically drive the neuronal activity in this structure. The opposite changes recorded in the ipsi- and contralateral subthalamic nucleus during unilateral microinjection of excitatory or inhibitory drugs in the parafascicular nucleus emphasize the importance of this thalamic structure in the bilateral regulation of basal ganglia activity via the subthalamic nucleus.