1. To examine the role of the subthalamic nucleus (STN) in the pathogenesis of dyskinesias, the STN was experimentally lesioned with fiber-sparing excitotoxins in two awake monkeys. 2. A combined recording-injection device was used to locate and lesion the STN accurately under physiological guidance. A small amount (1 microliters) of ibotenic acid (10 micrograms/microliters) or kainic acid (1 micrograms/microliters) was injected into each of four to seven target sites in the STN. Postmortem histology confirmed that lesions were confined to the STN, and the volume of each lesion at each site was 4-11% of the total volume of the nucleus. 3. Approximately 20 min after the end of each injection, the frequency of movements increased in the distal portions of the upper and lower limbs contralateral to the injection site. Severe dyskinesias, involving the proximal joints to a greater degree than the distal, developed in the contralateral limbs after 60-80 min and lasted < or = 4 h. The pattern of involvement and time course were similar after each lesion. In the days after the lesioning, only rare dyskinesias were observed in the contralateral hands and feet, typically occurring when the animals were stimulated. 4. Despite the severe dyskinesias, there was no obvious effect on voluntary movements such as grooming or reaching. 5. These results suggest that reduction of STN activity plays a role in the production of dyskinesias.