Adenosine is a nucleoside that plays an important role in the regulation of contractility in the heart. Adenosine receptors are G-protein coupled and those implicated in regulation of contractility are presumed to act via modulating the activity of adenylyl cyclase and cAMP content of cardiomyocytes. Adenosine A₁ receptors (A₁R) reduce the contractile response of the myocardium to β-adrenergic stimulation. This is known as anti adrenergic action. The A_2A adenosine receptor (A_2AR) has the opposite effect of increasing contractile responsiveness of the myocardium. The A_2AR also appears to attenuate the effects of A₁R. The effects of these receptors have been primarily studied in the rat heart and with the utilization of cardiomyocyte preparations. With the increasing use of receptor knockout murine models and murine models of various pathological states, it is of importance to comprehensively study the effects of adenosine receptors on regulation of contractility in the murine heart. The following studies examine the adenosinergic regulation of myocardial contractility in isolated murine hearts. In addition, adenosinergic control of contractility is examined in hearts isolated from A_2AR knockout animals. Responses to adenosinergic stimulation in murine isolated hearts are found to be comparable to those observed in the rat, with A₁R exhibiting an anti adrenergic action and A_2AR conversely enhancing contractility. A significant part of the A_2AR effect was found to occur via inhibition of the A₁R antiadrenergic action. A part of the anti adrenergic action of A₁R has previously been shown to be the result of protein phosphatase 2A activation and localization to membranes. Additional experiments in the present study examine the effect of adenosinergic signaling on PP2A in myocardial extracts from wild type and A_2AR knockout hearts. A_2AR activation was found to decrease the activity of PP2A and enhance localization of the active enzyme to the cytosol; away from its presumed sites of action. In the A_2AR knockout the response to A₁R activation was enhanced compared with the wild type and basal PP2A activity was reduced. It is concluded that A_2AR modulation of PP2A activity may account for the attenuation of the A₁R effect by A_2AR observed in the contractile studies.