Information about the neuropathology of spinal cord injury is derived from the personal study of 341 specimens; 225 of these were traumatic, including 123 with massive injuries. Thirty-one were associated with metastases, 38 were degenerative, and 6 were infectious. Included are 41 normal controls. The hyperacute human spinal injury study provides a reference base for animal experiments. A sound knowledge of the pathology of spinal injury is an essential prerequisite for the competent management of patients with these injuries. Because no lesions were found that would be amenable to surgical correction, the study supports the conservative approach, in keeping with the teaching and practice of Sir Ludwig Guttmann and Sir George Bedbrook. In most specimens traumatic necrosis was most severe in the central gray matter and adjoining posterior columns of the cord. Preserved continuity of a proportion of the lateral, anterior, and posterior white matter was usual. Space-taking subdural or extradural hemorrhages and hematomyelia were rare. In patients who survived for more than a few weeks, posttraumatic cysts resulted from removal of necrotic parenchyma by macrophages. Although in very severe injuries complete disruption of both bony and spinal cord tissues was observed, others with equally massive injuries showed some continuity of the spinal cord parenchyma. This somewhat unexpected observation is in accord with physiologic studies in which poly EMG and sensory-evoked potentials demonstrate continuity of long tracts across the lesion in patients who were otherwise clinically complete. Regeneration of nerve roots and to a lesser extent of central axons was evident in patients who survived for more than 5 or 6 months. Complications consisted of ascending or descending necrosis and enlarging cavities. There is clinical and physiologic evidence of remodeling of reflex systems in the spinal patient that manifests as a changing neurologic picture. It is possible that the use of a variety of techniques, such as electrical stimulation, would influence such plastic changes to the benefit of the patient. Little detailed anatomic information is available on this topic as a key area for future investigation.