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Activation of adenosine A_2A receptors (A_2AR) has been shown to antagonize the function of D₂ dopaminergic regulation of striatal γ‐aminobutyric acid (GABA)‐ergic output and, thus, locomotor activity. Adenosine A_2A receptor immunoreactivity (A_2A‐LI) has been localized to rat striatum by light microscopy by using a previously characterized human A_2AR monoclonal antibody. In this study, we evaluated the localization of A_2A‐LI and its colocalization with GABA immunoreactivity (GABA‐LI) in dorsolateral rat striatum by immunoelectron microscopy to further characterize the potential mechanism of purinergic control of striatal output. Ultrastructural analysis demonstrated A_2A‐LI associated with the plasma membrane and cytoplasmic membranous structures of striatal neurons. A_2A‐LI was prevalent in dendrites and dendritic spines (∼70% of total A_2A‐profiles counted) and less prevalent in axons and axon …