The purine nucleoside adenosine exerts numerous effects in the mammalian heart, the most well-recognized being regulation of coronary blood flow and cardiac conduction. These effects are mediated via activation of G protein linked adenosine receptor subtypes, A(2a) and A(1) receptors, located primarily on vascular cells and cardiac myocytes, respectively. Although adenosine A(1) receptors are also expressed in ventricular myocytes, adenosine exerts no significant direct effects in these cells. A recent report from our laboratory indicates that ventricular myocyte A(1) receptors are concentrated in caveolin enriched plasma membrane microdomains referred to as caveolae. This review focuses on these recent findings and their relevance to subcellular compartmentalization of A(1) receptor signaling in ventricular myocardium.