An interaction among leukocytes, platelets and endothelial cells is important in atherogenesis and in maintenance of blood flow and vascular tone. These complex cell-cell interactions are mediated by release of such metabolic substances as arachidonic acid metabolites, growth factors, oxygen free radicals and endothelium-derived relaxing factor. These substances participate in the regulation of blood flow in health and disease, and perturbation in the delicate equilibrium among various cellular elements may lead to evolution and propagation of myocardial ischemia. During reperfusion of ischemic myocardium, neutrophils together with platelets cause capillary plugging in the coronary microcirculation and exert detrimental effects on endothelial function resulting in the "no reflow" phenomenon, ventricular arrythmias, loss of coronary vascular reserve and, perhaps, extension of cellular injury. This review addresses the mechanisms of cell-cell interactions with special reference to myocardial ischemia and the potential for development of improved therapy to protect and preserve ischemic myocardium.