Systemic inflammation promotes multiple organ failure through the induction of diffuse microvascular leak. Inflammatory cells such as neutrophils propagate this process. Tissue injury by neutrophils may be viewed as a normal process, inflammation, that has become uncontrolled and generalized. Multiple inflammatory stimuli synergistically promote neutrophil-mediated tissue injury in priming and activation sequences. In some settings, cellular priming is mediated by platelet-activating factor and can be prevented by platelet-activating factor antagonists. Inhibiting cellular priming could be efficacious in the therapy of multiple organ failure.