The reduction of postischemic reperfusion injury by exogenous adenosine has been ascribed to reduced oxygen radical generation and adhesion of leukocytes to the vascular endothelium. To provide in vivo evidence for this concept we investigated the effects of adenosine (110 micrograms.kg-1.min-1 iv) on postischemic leukocyte-endothelium interaction in the dorsal skinfold chamber model in awake hamsters by intravital fluorescence microscopy. Leukocytes were stained in vivo with acridine orange and classified according to their interaction with the endothelium as nonadherent, rolling, or sticking leukocytes. In control animals, reperfusion after a 4-h pressure-induced ischemia to the striated muscle in the dorsal skinfold chamber elicited a marked increase in leukocyte rolling and sticking. This phenomenon was significantly attenuated in adenosine-treated animals 30 min after reperfusion. Postischemic changes in vessel diameters and red cell velocities were not affected by adenosine. The data suggest that systemic adenosine administration reduces reperfusion injury by the inhibition of postischemic leukocyte adherence to the microvascular endothelium.