Tissue ischemia of sufficient duration produces irreversible injury and cell death. Associated with the direct ischemic insult, there is an indirect attack on the jeopardized tissue through activation of the complement system. This activation, occurring in response to ischemia, facilitates neutrophil– endothelial cell interactions and neutrophil migration into and across the vascular wall, along with the formation of cytotoxic oxygen metabolites and release of proteolytic enzymes. The neutrophil–dependent actions participate in extending the tissue injury beyond that due to ischemia alone. The invading neutrophils injure the myocardial vasculature and sarcolemma through the generation of oxygen free radicals. Components of the complement system can damage tissue indirectly through formation of neutrophil chemoattractants as well as directly through assembly of the cytolytic “membrane attack complex.” As is the case with any organ, function and cellular viability are dependent upon a blood supply, which, if interrupted for a sufficiently long period, will lead to progressive irreversible cellular changes and necrosis. Thus, arrest of the ischemic process demands that blood flow be restored. It is this self-evident truth which gives rise to a paradox that has aroused the interest of basic scientists and clinicians attempting to comprehend and control the phenomenon of reperfusion injury...