Adenosine can induce vasodilatation and vasoconstriction of the renal afferent arteriole of the mouse. We determined here its direct effect on efferent arterioles of mouse kidneys. Using isolated-perfused cortical efferent arterioles, we measured changes in luminal diameter in response to adenosine. Extraluminal application of adenosine and cyclohexyladenosine had no effect on the luminal diameter. When the vessels were constricted by the thromboxane mimetic U46619, application of adenosine and 5'-N-ethylcarboxamido-adenosine dilated the efferent arterioles in a dose-dependent manner. We also found that the adenosine-induced vasodilatation was inhibited by the A(2)-specific receptor blocker 3,7-dimethyl-1-propargylxanthine. In the presence of this inhibitor, adenosine failed to alter the basal vessel diameter of quiescent efferent arterioles. Using primer-specific polymerase chain reaction we found that the adenosine A(1), A(2a), A(2b), and A(3) receptors were expressed in microdissected mouse efferent arterioles. We conclude that adenosine dilates the efferent arteriole using the A(2) receptor subtype at concentrations compatible with activation of the A(2b) receptor.