This report discusses the development of brain injury tolerance criteria based on the study of three model systems: the primate, inanimate physical surrogates, and isolated tissue elements. Although we are equally concerned with the neural and neurovascular tissue components of the brain, the report will focus on the former and, in particular, the axonal elements. Under conditions of distributed, impulsive, angularacceleration loading, the primate model exhibits a pathophysiological response ranging from mild cerebral concussion to massive, diffuse white matter damage with prolonged coma. When physical models are subjected to identical loading conditions it becomes possible to map the displacements and calculate the associated strains and stresses within the field simulating the brain. Correlating these experimental models leads to predictive levels of tissue element deformation that may be considered as a threshold for specific mechanisms of injury. Isolated tissue studies in the axon then serve to confirm the relationship between ultimate strain, for example, and the pathophysiological consequences. At this time, we have found that elongating strains of between 5 and 10 percent at strain rates of greater than 50sec−1 produce membrance depolarization and a concomitant decrease in excitability that recovers in minutes. The degree of depolarization is directly proportional to the magnitude of the stretch. Further, total structural failure of the axonal membrane (diameters 400-750.jmm) occurs between 25 and 50 percent elongation at comparable strain rates. These observations are in reasonable agreement with the estimations of critical strains obtained from the primate and physical model studies.