A new experimental model of mechanical brain injury was produced in the laboratory ferret (Mustela putorius furo) using a stroke-constrained pneumatic impactor. Cortical impacts were made on vertex to the intact dura mater overlying the cerebral cortex with contact velocities ranging from 2.0 to 4.0 m/sec and with deformations of 2.0 to 5.0 mm. The dwell time of the impact and the stability of the skull during impact were verified with high speed (1000 to 3000 frames/sec) cineradiography. Systemic arterial blood pressure, heart rate, and respiration were monitored, and postinjury changes were recorded. Anatomic brain injury, including subdural hematoma, subarachnoid hemorrhage, tears or rents of the dura mater, and contusions of the cortex, brainstem, cervical spinal cord, and cerebellum was observed. Injury responses ranged from no apparent anatomic injury or alterations in the systemic physiology at low severity impact (2.0 m/sec, 2.0 mm) to immediate fatality in the highest severity impact groups (4.0 m/sec, 4.0 mm). The range of changes in systemic physiology and of pathology in the brain, brainstem, and spinal cord was a function of both contact velocity and the amount of brain deformation. In two cases where postinjury time was 8-10 h, diffuse axonal injury, indicated by beaded axons and retraction balls, was present in subcortical regions underlying the site of impact. The spectrum of anatomic injury and systemic physiologic responses closely resembled aspects of closed head injury seen clinically. This procedure complements and improves on existing techniques by allowing independent control of contact velocity and level of deformation of the brain to facilitate biomechanical and analytic modeling of brain trauma. Graded cortical contusions and subcortical injury are produced by precisely controlled brain deformations, thereby allowing questions to be addressed regarding the influence of contact velocity and level of deformation on the anatomic and functional severity of brain injury.