The enhanced behavioural response to repeated dopamine (DA)-replacement therapy seen in the 6-hydroxidopamine (6-OHDA)-lesioned rats has pharmacological characteristics similar to 3,4 dihydroxyphenyl-L-alanine (L-DOPA) induced dyskinesia (Henry et al., 1998; Lundblat et al., 2002). The neural mechanisms underlying L-DOPA-induced dyskenesia remain unknown. Nitric oxide (NO) has been proposed as a new neurotransmitter in the nervous system. Inhibition of NO synthase (NOS) induces an impairment of exploratory and motor behaviour and give support to the hypothesis that NO plays a role in motor behaviour control (Del Bel & Guimaraes, 2001). In addition results have shown an interaction between NO system and induced neurodegenerative process in nigrostriatal pathway (Gomes & Del Bel, 2003). In these experiments we examined the effects of an inhibitor of NOS on L-DOPA-induced-rotational behaviour in the 6-OHDA-lesioned rats and compare it to that of L-DOPA-induced dyskinesia. The experiments were carried out according to the Brazilian Society of Neuroscience and Behaviour guidelines for care and use of Laboratory animals. Male albino-Wistar rats (180-200 g) were housed in groups, in a temperature-controlled room with a 12-hour light/dark cycle, with free access to food and water. Rats with unilateral 6-OHDA lesions received single daily injections of L-DOPA (oral, 100mg/kg plus 15 mg/kg benserazide) for three weeks. The rats gradually developed abnormal involuntary movements, lasting 2-3 h following each L-DOPA dose. L-DOPA-induced rotation/2 h (1060.57±197.46) was potentiated by the acute administration of the NOS inhibitor NG-nitro-L-arginine (L-NOARG, 50 mg/kg i.p.; 1746.28±261.58)) in 6-OHDA-lesioned rats. In contrast following priming by L-DOPA replacement therapy, administration of L-NOARG reduced L-DOPA-induced rotation/2 h (control=1156.8±350.52; L-NOARG=550±279.39). Within the L-DOPA-treated group, levels of NOS neurons in DA-denervated dorsal ipsilateral-striatum were higher in dyskinetic than in non-dyskinetic animals (NOS-neurons/100 μm², control=5.33±0.88; test=8.79±0.79). The results suggest that NOS-inhibitors may have anti-dyskinesogenic potential in Parkinson disease. It shown that L-DOPA-induced dyskinesia is associated with over-expression of NOS in the striatal projection neurons. Due to its treatment-dependent expression, striatal NOS may play a role in the mechanisms of behavioural sensitization brought about by the drug.