Microcirculatory derangements in organ transplantation, characterized by capillary perfusion failure and inflammation-associated leukocyte recruitment, are major determinants for the manifestation of graft dysfunction and destruction. Although preservation/cold storage, posttransplant reperfusion, and rejection have to be considered as individual factors that contribute to injury, recent studies have indicated that ischemia-reperfusion-associated events may trigger immune-response-mediated late rejection. There is major evidence that the microcirculatory derangements induced by cold preservation and reperfusion involve oxygen radicals, complement, phospholipase A2, leukotrienes, thromboxane, platelet-activating factor, and endothelin-1 as well as the activation and function of leukocytic and endothelial selectins, beta 2-integrins, and ICAM-1. This view is based on the fact that blockade or neutralization of these inflammatory mediators and adhesion molecules results in significant amelioration of microvascular graft dysfunction. In parallel, rejection-mediated microcirculatory derangements may not only be ameliorated by immunosuppressive agents, such as cyclosporin, deoxyspergualin, or RS61443, but may, in addition, effectively be inhibited by counteracting oxygen radicals, complement, platelet-activating factor, and adhesion molecules. The introduction of novel techniques for the study of the microcirculation in men, such as thermodiffusion and orthogonal polarization spectral imaging, may in the future assist in improving both early diagnosis of microcirculatory derangements and monitoring of appropriateness of therapy in clinical transplantation surgery.