<i>Background/Aims:</i> A structural and functional interaction between A_2A adenosine receptors and D₂ dopamine receptors has been implicated in the pathophysiology of impulse control disorders. The aim of this study was to use platelet membranes to assess A_2A adenosine receptor affinity and density in patients affected by pathological gambling (PG; which is classified as a specific impulse control disorder) with respect to those of control subjects. <i>Methods:</i> Twelve drug-free PG patients and 12 age- and sex-matched healthy controls were enrolled in the study. PG was diagnosed according to the Structured Clinical Interview for DSM-IV – Patient Version 2.0 and the South Oaks Gambling Screen. A_2A adenosine receptor binding parameters were evaluated using a [³H]ZM₂₄₁₃₈₅ binding assay; affinity and density (B_max) were determined by means of saturation binding studies with platelet membranes. <i>Results:</i> The A_2A adenosine receptor binding affinity was found to be significantly higher in patients affected by PG than in healthy subjects; in contrast, no significant differences in B_max were observed between the 2 groups. <i>Conclusions: </i>The elevated A_2A adenosine receptor binding affinity in platelets from PG patients with respect to control subjects demonstrates for the first time a change in adenosine receptor parameters, and it suggests the involvement of the adenosine system in this pathology. The previously demonstrated hyperactivity of the dopamine system in PG may modulate the A_2A adenosine receptor, supporting a role for this receptor as a peripheral marker of dopamine dysfunction. Because it is not possible to directly measure the D₂ dopamine receptor in human platelets, these data are particularly relevant to the detection of dopamine dysfunction.