Nitric oxide is highly mobile and unconstrained by cell membranes. As such, it can therefore act across abroad distance as a volume transmitter. Spillover of nitric oxide between neurons might have a major impact on central nervous system diseases and particularly on neurodegeneration. In this sense, there is abundant evidence indicating that the communication between nitrergic and dopaminergic systems plays an essential role in the control of motor function. Dopaminergic boutons represent nearly 10% of all striatal synapses (Arbuthnott and Wickens 2007). The release of a single vesicle of dopamine could modulate the excitability of tens to thousands of synapses within distances a few micrometers of a release site, in both substantia nigra compacta and striatum (Cragg et al., 2001).It is predicted that the physiological volume of influence of a single source of nitric oxide that emits for 1 to 10 seconds has a diameter of about 200 mm, corresponding to a volume of brain enclosing 2 million synapses (Wood and Garthwaite 1994). However, there is sparse information available for either the coexistence or overlap between nitric oxide and dopamine in the nigrostriatal region, which in turn may be a mechanism of functional significance. The dual localization of immunoreactivity for nitric oxide synthase and tyrosine hydroxylase, enzymes responsible for the synthesis of nitric oxide and dopamine, respectively, in the neurons of the nigrostriatal pathway in the rat brain was examined by means of a double-immunohistochemical method and confocal laser scanning microscopy. The study was performed on six adult Wistar rats. After perfusion and fixation, the brains were cut, immuno- stained for tyrosine hydroxylase and nitric oxide synthase. We investigated neuronal populations in the frontal cortex, striatum (ventral and dorsal), globus pallidus, subthalamic nuclei, substantia nigra and in the pedunculopontine nuclei. High-resolution confocal laser scanning microscopy revealed nitric oxide synthase immunoreactive fiber buttons in submicrometer proximity to both the axon/dendrite and soma of tyrosine hydroxylase immunoreactive neurons and fibers of each studied region. Among them, a considerable number showed close proximity of both neurotransmitters. Only a small portion of the widely co-distributed cells was double labeled with both antibodies. Pharmacological manipulation of nitric oxide signaling affected the response of experimental Parkinsonism (Gomes et al., 2008) and levodopa-induced dyskinesia (Padovan-Neto et al., 2009). 1). Based (i) on the localization of tyrosine hydroxylase- nitric oxide synthase-positive processes/neuronal body and vice versa, and (ii) the similar physiological responses effected in pharmacological studies of either transmitter system in the nigrostriatal organization, we have identified anatomical/physiological sites where the two neurotransmitter types interact with each other.