Multiple organ failure remains a leading cause of death in surgical intensive care units. This review of multiple organ failure focuses on recent (1990 to 1992) laboratory and clinical advances related to diagnosis, prognosis, and therapy of multiple organ failure and is divided into three parts. First, it recasts multiple organ failure into the currently accepted terminology, ie, the multiple organ dysfunction syndrome. Second, it examines the strengths and weaknesses of three mechanistic hypotheses proposed for the clinical syndrome. The three hypotheses focus on the gut, molecular mediators, and the microvasculature. Third, it synthesizes those three mechanisms into a single paradigm; this unifying paradigm can serve as a framework in which to interpret subsequent laboratory and clinical advances.