Adenosine participates in the physiology of central and peripheral tissues through several subtypes of G-protein-coupled receptors. Positively linked to adenylate cyclase, A2 receptors have been subdivided into A2a and A2b sites on the basis of their molecular, biochemical and pharmacological properties. They exhibit selective distribution, and are implicated in the modulation of psychomotor activity, circulation, respiration, and metabolism. Recent data support the evidence that adenosine A2 receptor properties may prove useful in future drug development, and selective manipulation of receptor-associated biologic effects might be relevant in the treatment of various disorders, including psychiatric diseases, hypoxia/ischemia, inflammation or erythrocytosis.