GLIAL fibrillary acidic protein (GFAP) is an intermediate filament protein expressed primarily in astrocytes. We have tested whether GFAP protects against mechanical stress by inducing percussive head injury in GFAP-null mice with a weight drop device. When mice were positioned on a foam bed which allowed head movement at impact, all 14 wild-type mice tested survived, but 12 of 15 GFAP-null mice died within a few minutes. The cause of death appeared to be upper cervical spinal cord injury resulting in respiratory arrest. When the foam bed was replaced by a firm support, both GFAP-null and wild-type mice survived. These results indicate that mice lacking GFAP are hypersensitive to cervical spinal cord injury caused by sudden acceleration of the head.