['Skeletal muscle reperfusion injury is mediated by IgM natural antibodies and by complement activation, as shown by the attenuation of reperfusion injury seen in mice with no natural IgM [] and in mice deficient in complement C3 and C4 []. We postulate that tissue, when ischemic, expresses neoantigens to which preformed natural IgM antibodies bind, in turn producing harmful complement activation and reperfusion injury.', 'C57Bl/6 mice were subjected to 2 h of tourniquet-induced hind limb ischemia followed by variable periods of reperfusion. Two hours of ischemia and 3 h of reperfusion produced severe muscle necrosis and edema. Deposition of IgM and C3 in tissue was assessed using immunohistochemistry on both frozen and Formalin-fixed tissue samples.', 'IgM binding to the endothelium and muscle bundles of the hind limb began during the ischemic period and continued throughout reperfusion up to 6 h. C3 deposition was not present during ischemia and, in contrast, began to appear at 1 h of reperfusion and increased progressively thereafter.'] Does igM binding to injured tissue precede complement activation during skeletal muscle ischemia-reperfusion?