Myocellular injury induced by acute ischemia and subsequent reperfusion was studied in 38 dogs, with special reference to sarcolemmal permeability as determined by the vital ionic lanthanum (La3+) probe technique and electron microscopy. The left anterior descending coronary artery (LAD) was occluded in 14 dogs for 10 to 60 min, and the ischemic zone was perfused slowly for 7 min with a La(3+)-containing solution. In 21 dogs, the LAD was released for 10 min after occlusion and was then reperfused for 7 min with arterial blood plus the La(3+)-containing solution. Subsequently, in both groups of animals, the ischemic myocardium was subjected to perfusion fixation in preparation for electron microscopy. In normal cardiac myocytes, La3+ was localized exclusively in the extracellular space. After 10 to 20 min of ischemia, more than 80% of myocytes appeared normal or were damaged only slightly, and the majority continued to exclude La3+. After 10 min of ischemia, deposits of lanthanum were detected in 1 and 6% of myocytes in the absence or presence of reperfusion, respectively. The number of cells with such deposits was markedly increased after 30 min of ischemia (19%), as well as after 20 min of ischemia followed by reperfusion (17%), prior to the development of irreversible myocardial damage. After 60 min of ischemia with or without reperfusion, about 30% of myocytes showed severe injury with particulate deposits of lanthanum throughout the entire cell. These results indicate that sarcolemmal permeability increases during the early stage of myocardial injury due to ischemia or ischemia-reperfusion and contributes to the development of myocardial damage.