It has been previously found that the systemic administration of low doses of N-methyl-D-aspartate (NMDA) in mice induces motor depression. The effects of the systemic administration of different doses of NMDA (10, 30 and 60 mg/kg s.c.) on the motor activity and on the in vivo extracellular levels of adenosine in the striatum was studied in Sprague-Dawley rats. The adenosine concentration in samples of perfusate was determined 24 h after implantation of a transverse microdialysis probe. At 30 and 60 mg/kg, but not 10 mg/kg, NMDA induced both a significant motor depression (motility and rearing) and a significant increase in the striatal extracellular levels of adenosine. Both the motor depression and the changes in the extracellular levels of adenosine were only evident during the first 30 min after NMDA administration. The non-competitive NMDA receptor antagonist MK-801 (0.1 mg/kg s.c.) completely counteracted the effects of NMDA (30 mg/kg s.c.) on motor activity (motility) and on the striatal extracellular levels of adenosine. The correlation between the behavioural and the biochemical data strongly support the hypothesis that adenosine release in the striatum is a main mechanism responsible for the motor depressant effects produced by the systemic administration of NMDA.