Explosive blast has been extensively used as a tactical weapon in Operation Iraqi Freedom (OIF) and more recently in Operation Enduring Freedom (OEF). The polytraumatic nature of blast injuries is evidence of their effectiveness, and brain injury is a frequent and debilitating form of this trauma. In-theater clinical observations of brain-injured casualties have shown that edema, intracranial hemorrhage, and vasospasm are the most salient pathophysiological characteristics of blast injury to the brain. Unfortunately, little is known about exactly how an explosion produces these sequelae as well as others that are less well documented. Consequently, the principal objective of the current report is to present a swine model of explosive blast injury to the brain. This model was developed during Phase I of the DARPA (Defense Advanced Research Projects Agency) PREVENT (Preventing Violent Explosive Neurotrauma) blast research program. A second objective is to present data that illustrate the capabilities of this model to study the proximal biomechanical causes and the resulting pathophysiological, biochemical, neuropathological, and neurological consequences of explosive blast injury to the swine brain. In the concluding section of this article, the advantages and limitations of the model are considered, explosive and air-overpressure models are compared, and the physical properties of an explosion are identified that potentially contributed to the in-theater closed head injuries resulting from explosions of improvised explosive devices (IEDs).